ALBERT

Description:    Characterization of matrix metalloprotease (MMP) activities is of increasing interest for cancer prognosis or treatment follow-up. Indeed, MMP-1, -2 and -9 are widely involved in the growth of many tumors and progression steps such as angiogenesis, invasion, and metastasis. Fluorogenic peptide MMP substrates were previously synthesized with the aim of detecting MMP activities. One of their drawbacks is their limited solubility in biological media. Grafting them onto a solid support represented a novel way to yield efficient analysis devices whilst at the same time decreasing the quantities of peptides used. Novel peptide arrays were designed in order to detect MMP activities in biological fluids. Silicon plates were used as the solid support for the design of these novel tools. These were functionalized by organic self-assembled monolayers (SAMs) on which fluorogenic peptides were covalently coupled. SAM and peptide grafting on silicon plates were confirmed by epifluorescence, ellipsometry, and FT-IR analysis. Enzymatic assays were monitored by fluorescence spectrometry and showed that immobilized linear peptides were recognized and cleaved by MMPs. Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s00216-012-5760-x Authors Mohamed-Anis Alouini, Université Bordeaux Segalen, CNRS, FRE 3396 Pharmacochimie, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France El-Farouck Moustoifa, Université Bordeaux Segalen, CNRS, FRE 3396 Pharmacochimie, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France Sandra Albenque Rubio, Université Bordeaux Segalen, CNRS, FRE 3396 Pharmacochimie, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France Aghleb Bartegi, Unité de Recherche 02/UR/09-01 Biochimie des Protéines et Interactions Moléculaires, Avenue Taher Hadda, BP 74, Monastir, 5000 Tunisia Thomas Berthelot, Chemistry of Surfaces and Interfaces CEA Saclay, Bâtiment 466, F-91191 Gif-sur-Yvette, CEDEX, France Gérard Déléris, Université Bordeaux Segalen, CNRS, FRE 3396 Pharmacochimie, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Environmental analysis most often is trace analysis. Therefore, the concentrations are commonly in the lower working range near the limit of detection of the corresponding analytical method. However, whenever the instrument’s analytical noise is too large, it dominates the signal curves and analytes cannot be detected anymore. Furthermore, the evaluation of peaks with defined baselines is hindered very much. One possibility for de-noising is wavelet transform which is presented in this work. Different wavelet functions are applied and Symlet4 is suggested as the most powerful for analytical peaks that resemble Gaussian distribution curves, as it improves limits of detection by factors 6 to 7. The comparison of different wavelet functions has been carried out for two modern analytical scopes. At first, chromatograms are de-noised for the speciation of four arsenic compounds via the coupling of HPLC and ICP-MS. Secondly, the determination of cadmium is shown by HR-CS AAS, which is one of the most recently developed devices in atomic absorption spectrometry and allows the registration of three-dimensional spectra in order to investigate the spectral vicinity of analytical lines. On the basis of these investigations, we recommend using wavelet transform with Symlet4 for all analytical techniques which are resulting in similar signal curves. Content Type Journal Article Category Technical Note Pages 1-5 DOI 10.1007/s00216-012-5828-7 Authors Simon Prikler, Department of Environmental Analysis, Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University of Jena, Lessingstraße 8, 07743 Jena, Germany Jürgen W. Einax, Department of Environmental Analysis, Institute of Inorganic and Analytical Chemistry, Friedrich Schiller University of Jena, Lessingstraße 8, 07743 Jena, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Columns containing immobilized low-density lipoprotein (LDL) were prepared for the analysis of drug interactions with this agent by high-performance affinity chromatography (HPAC). R/S -Propranolol was used as a model drug for this study. The LDL columns gave reproducible binding to propranolol over 60 h of continuous use in the presence of pH 7.4 0.067 M potassium phosphate buffer. Experiments conducted with this type of column through frontal analysis indicated that two types of interactions were occurring between R -propranolol and LDL, while only a single type of interaction was observed between S -propranolol and LDL. The first type of interaction, which was seen for both enantiomers, involved non-saturable binding; this interaction had an overall affinity ( nK a ) of 1.9 (±0.1) × 10 5  M −1 for R -propranolol and 2.7 (±0.2) × 10 5  M −1 for S -propranolol at 37 °C. The second type of interaction was observed only for R -propranolol and involved saturable binding that had an association equilibrium constant ( K a ) of 5.2 (±2.3) × 10 5  M −1 at 37 °C. Similar differences in binding behavior were found for the two enantiomers at 20 °C and 27 °C. This is the first known example of stereoselective binding of drugs by LDL or other lipoproteins. This work also illustrates the ability of HPAC to be used as a tool for characterizing mixed-mode interactions that involve LDL and related binding agents. Online abstract figure  Potential routes for drug interactions with low density lipoprotein (LDL). Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-5816-y Authors Matthew R. Sobansky, Chemistry Department, University of Nebraska, Lincoln, NE 68588-0304, USA David S. Hage, Chemistry Department, University of Nebraska, Lincoln, NE 68588-0304, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    We report the development of a National Institute of Metrology (NIM) hemoglobin A 1c (HbA 1c ) certified reference material (CRM). Each CRM unit contains about 10 μL of hemoglobin. Both hemoglobin and glycated hemoglobin were quantitatively determined by high-performance liquid chromatography (HPLC)–isotope dilution mass spectrometry (IDMS) with synthesized VHLTPE and glycated VHLTPE as standards. The mass fraction of synthesized VHLTPE or glycated VHLTPE was also quantitatively determined by HPLC-IDMS with NIM amino acid CRMs as standards. The homogeneity and stability of the CRMs were examined with a commercial HbA 1c analyzer based on the HPLC principle. Fifteen units were randomly selected for homogeneity examination, and statistical analysis showed there was no inhomogeneity. Examination of the stability showed that the CRM was stable for at least 6 months at -80 °C. Uncertainty components of the balance, amino acid purity, hydrolysis and proteolysis efficiency, method reproducibility, homogeneity, and stability were taken into consideration for uncertainty evaluation. The certified value of NIM HbA 1c CRM was expressed as the ratio of HbA 1c to total hemoglobin in moles, and was (9.6 ± 1.9)% . The CRM can be used as a calibration or validation standard for clinical diagnostics. It is expected to improve the comparability for HbA 1c measurement in China. Content Type Journal Article Category Original Paper Pages 1-6 DOI 10.1007/s00216-012-5834-9 Authors Jiaming Bi, College of Science, Beijing University of Chemical Technology, Beijing, 100029 China Liqing Wu, Division of Biological, Energy and Environmental Measurement, National Institute of Metrology, Beijing, 100013 China Bin Yang, Division of Biological, Energy and Environmental Measurement, National Institute of Metrology, Beijing, 100013 China Yi Yang, College of Science, Beijing University of Chemical Technology, Beijing, 100029 China Jing Wang, Division of Biological, Energy and Environmental Measurement, National Institute of Metrology, Beijing, 100013 China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Erratum to: Analytical methods for determination of new fluoroquinolones in biological matrices and pharmaceutical formulations by liquid chromatography: a review Content Type Journal Article Category Erratum Pages 1-1 DOI 10.1007/s00216-012-5913-y Authors Joana Sousa, Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal Gilberto Alves, CNC – Centre for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal João Abrantes, Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal Ana Fortuna, Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal Amílcar Falcão, Pharmacology Department, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: 10th Dresdner Sensor-Symposium—an anniversary to celebrate Content Type Journal Article Category Conference Highlights Pages 1-2 DOI 10.1007/s00216-012-5842-9 Authors Melanie Ewald, Group Optical Spectroscopy, Institute of Physical and Theoretical Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany Barbara Schwarz, Group Optical Spectroscopy, Institute of Physical and Theoretical Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    In the last years, some analytical methodologies have been identified as a source of pollution, receiving increasing attention to decrease their impact on the environment. In this sense, the so-called solvent-less methodologies appear as a green alternative to reduce the volume of solvents used in many sample treatment procedures and, consequently, the volume of toxic wastes produced. Among these techniques, analytical methodologies based on liquid-phase microextraction are being continuously developed, although most applications are focused on organic compounds. In this work, a three-phase hollow-fibre liquid-phase microextraction (HF-LPME) system has been developed for the preconcentration of nickel in natural waters, prior to the analysis by atomic absorption spectrometry. Under optimum conditions, the new system allowed an enrichment factor of 29.80 to be obtained after 60 min of experiment, and it was successfully applied to the determination of nickel in both saline and non-saline water samples, at ppb and ppt levels. The results were compared with those obtained using a well-established methodology based on liquid solvent extraction showing no significant differences ( α  = 0.05) between both values. In addition, the new HF-LPME presents the advantages of a green analytical technique, as its greenness profile shows, with the additional reduction of sample manipulation and time cost. Content Type Journal Article Category Original Paper Pages 1-6 DOI 10.1007/s00216-012-5896-8 Authors Cristina Vergel, Department of Analytical Chemistry, Faculty of Marine and Environmental Sciences, University of Cádiz, 11510 Puerto Real, Spain Rocío Montoya, Department of Analytical Chemistry, Faculty of Chemistry, University of Sevilla, 41012 Sevilla, Spain Carolina Mendiguchía, Department of Analytical Chemistry, Faculty of Marine and Environmental Sciences, University of Cádiz, 11510 Puerto Real, Spain Manuel García-Vargas, Department of Analytical Chemistry, Faculty of Marine and Environmental Sciences, University of Cádiz, 11510 Puerto Real, Spain Carlos Moreno, Department of Analytical Chemistry, Faculty of Marine and Environmental Sciences, University of Cádiz, 11510 Puerto Real, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Mass spectrometry (MS)-based enzyme assay has been shown to be a useful tool for screening enzymatic activities from environmental samples. Recently, reported approaches for high-specificity multiplexed characterization of enzymatic activities allow for providing detailed information on the range of enzymatic products and monitoring multiple enzymatic reactions. However, the throughput has been limited by the slow liquid–liquid handling and manual analysis. This rapid communication demonstrates the integration of acoustic sample deposition with nanostructure initiator mass spectrometry (NIMS) imaging to provide reproducible measurements of multiple enzymatic reactions at a throughput that is tenfold to 100-fold faster than conventional MS-based enzyme assay. It also provides a simple means for the visualization of multiple reactions and reaction pathways. Content Type Journal Article Category Short Communication Pages 1-5 DOI 10.1007/s00216-012-5908-8 Authors Matthew Greving, Nextval, 4186 Sorrento Valley Blvd, Suite G, San Diego, CA 92121, USA Xiaoliang Cheng, Department of Bioenergy/GTL and Structural Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94704, USA Wolfgang Reindl, Department of Bioenergy/GTL and Structural Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94704, USA Benjamin Bowen, Department of Bioenergy/GTL and Structural Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94704, USA Kai Deng, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Joint BioEnergy Institute (JBEI), Berkeley, CA 94720, USA Katherine Louie, Department of Bioenergy/GTL and Structural Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94704, USA Michael Nyman, Nextval, 4186 Sorrento Valley Blvd, Suite G, San Diego, CA 92121, USA Joseph Cohen, Nextval, 4186 Sorrento Valley Blvd, Suite G, San Diego, CA 92121, USA Anup Singh, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Joint BioEnergy Institute (JBEI), Berkeley, CA 94720, USA Blake Simmons, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Joint BioEnergy Institute (JBEI), Berkeley, CA 94720, USA Paul Adams, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Joint BioEnergy Institute (JBEI), Berkeley, CA 94720, USA Gary Siuzdak, Department of Chemistry, Center for Metabolomics, The Scripps Research Institute, La Jolla, CA 92037, USA Trent Northen, Department of Bioenergy/GTL and Structural Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94704, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Many chromophores absorb light intensely but have undetectable fluorescence. Hence microscopy techniques other than fluorescence are highly desirable for imaging these chromophores inside live cells, tissues, and organisms. The recently developed pump-probe optical microscopy techniques provide fluorescence-free contrast mechanisms by employing several fundamental light–molecule interactions including excited state absorption, stimulated emission, ground state depletion, and the photothermal effect. By using the pump pulse to excite molecules and the subsequent probe pulse to interrogate the created transient states on a laser scanning microscope, pump-probe microscopy offers imaging capability with high sensitivity and specificity toward nonfluorescent chromophores. Single-molecule sensitivity has even been demonstrated. Here we review and summarize the underlying principles of this emerging class of molecular imaging techniques. Figure  Apparatus used for pump-probe microscopy Content Type Journal Article Category Review Pages 1-6 DOI 10.1007/s00216-012-5890-1 Authors Lu Wei, Department of Chemistry, Columbia University, New York, NY 10027, USA Wei Min, Department of Chemistry, Columbia University, New York, NY 10027, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Benzotriazoles are a group of UV absorbing compounds considered emerging contaminants that are used in different personal care products, and therefore, it is of high interest to develop sensitive and fast methods for investigating their presence in the environment. In this work, we present the development and application of a novel method based on on-line solid-phase extraction coupled to ultra-performance liquid chromatography with tandem mass spectrometry detection (SPE-UPLC-MS/MS) for the determination of seven benzotriazole UV stabilizers (BUVSs) in coastal marine and wastewater samples. This process is compared with a conventional off-line SPE procedure followed by UPLC-MS/MS. The parameters affecting the performance of the sample preparation and determination processes were evaluated. The results indicate that the on-line procedure provides for better sensitivity and reproducibility and is faster and easier than the off-line procedure. The detection limits and quantification limits achieved were in the range of 0.6–4.1 ng∙L −1 and 2.1–14 ng∙L −1 and relative standard deviation between 6.2 and 10 %. The developed method was applied to coastal marine and wastewater samples from Gran Canaria Island (Spain). All of the BUVSs studied were detected in the samples from wastewater treatment plants and two were found in the seawater samples (UV P in the range of 2.8–4.4 ng∙L −1 and UV 360 between 3.6 and 5.2 ng∙L −1 ). Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s00216-012-5906-x Authors Sarah Montesdeoca-Esponda, Departamento de Química, Universidad de Las Palmas de Gran Canaria, 35017 Las Palmas de Gran Canaria, Spain Zoraida Sosa-Ferrera, Departamento de Química, Universidad de Las Palmas de Gran Canaria, 35017 Las Palmas de Gran Canaria, Spain José Juan Santana-Rodríguez, Departamento de Química, Universidad de Las Palmas de Gran Canaria, 35017 Las Palmas de Gran Canaria, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Novel molecularly imprinted polymer (MIP)-coated fibers for solid-phase microextraction (SPME) fibers were prepared by using linezolid as the template molecule. The characteristics and application of these fibers were investigated. The polypyrrole, polythiophene, and poly(3-methylthiophene) coatings were prepared in the electrochemical polymerization way. The molecularly imprinted SPME coatings display a high selectivity toward linezolid. Molecularly imprinted coatings showed a stable and reproducible response without any influence of interferents commonly existing in biological samples. High-performance liquid chromatography with spectroscopic UV and mass spectrometry (MS) detectors were used for the determination of selected antibiotic drugs (linezolid, daptomycin, amoxicillin). The isolation and preconcentration of selected antibiotic drugs from new types of biological samples (acellular and protein-free simulated body fluid) and human plasma samples were performed. The SPME MIP-coated fibers are suitable for the selective extraction of antibiotic drugs in biological samples. Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s00216-012-5901-2 Authors Malgorzata Szultka, Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7 Street, 87-100 Torun, Poland Jacek Szeliga, Department of General, Gastroenterological and Oncological Surgery, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Joseph Street 53-59, 85-067 Bydgoszcz, Poland Marek Jackowski, Department of General, Gastroenterological and Oncological Surgery, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Joseph Street 53-59, 85-067 Bydgoszcz, Poland Boguslaw Buszewski, Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7 Street, 87-100 Torun, Poland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Anthocyanins are naturally occurring compounds that impart color to fruits, vegetables, and plants, and are believed to have a number of beneficial health effects in both humans and animals. Because of these properties, pharmacokinetic analysis of anthocyanins in tissue has been performed to quantify and identify anthocyanin species although, currently, no methods exist for investigating tissue localization of anthocyanin species or for elucidating the mechanisms of anthocyanin activity. Imaging mass spectrometry (IMS) is powerful tool for determining and visualizing the distribution of a wide range of biomolecules. To investigate whether anthocyanin species could be identified and visualized by IMS, we performed matrix-assisted laser desorption/ionization (MALDI)–IMS analysis, by tandem mass spectrometry (MALDI–IMS–MS), of ten anthocyanin molecular species in rabbiteye blueberry ( Vaccinium ashei ). The distribution patterns of each anthocyanin species were different in the exocarp and endocarp of blueberry sections. Anthocyanin species composed of delphinidin and petunidin were localized mainly in the exocarp. In contrast, those species composed of cyanidin, peonidin, and malvidin were localized in both the exocarp and the endocarp. Moreover, MALDI–IMS analysis of anthocyanidins in a blueberry section indicated that the distribution patterns of each anthocyanidin species were nearly identical with those of the corresponding anthocyanins. These results suggested that the different distribution patterns of anthocyanin species in the exocarp and endocarp depended on the aglycone rather than on the sugar moieties. This study is the first to visualize anthocyanin molecular species in fruits. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-5876-z Authors Yukihiro Yoshimura, Department of Applied Biological Chemistry, Graduate School of Agriculture, Kinki University, 3327-204 Naka-machi, Nara, 631-8505 Japan Hirofumi Enomoto, Department of Biosciences, Faculty of Science and Engineering, Teikyo University, Utsunomiya, Tochigi 320-8551, Japan Tatsuya Moriyama, Department of Applied Biological Chemistry, Graduate School of Agriculture, Kinki University, 3327-204 Naka-machi, Nara, 631-8505 Japan Yukio Kawamura, Department of Applied Biological Chemistry, Graduate School of Agriculture, Kinki University, 3327-204 Naka-machi, Nara, 631-8505 Japan Mitsutoshi Setou, Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan Nobuhiro Zaima, Department of Applied Biological Chemistry, Graduate School of Agriculture, Kinki University, 3327-204 Naka-machi, Nara, 631-8505 Japan Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Euroanalysis XVI—challenges in modern analytical chemistry Content Type Journal Article Category Editorial Pages 1-3 DOI 10.1007/s00216-012-5884-z Authors Slavica Ražić, Department of Analytical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Because cerebrospinal fluid (CSF) is the biofluid which interacts most closely with the central nervous system, it holds promise as a reporter of neurological disease, for example multiple sclerosis (MScl). To characterize the metabolomics profile of neuroinflammatory aspects of this disease we studied an animal model of MScl—experimental autoimmune/allergic encephalomyelitis (EAE). Because CSF also exchanges metabolites with blood via the blood–brain barrier, malfunctions occurring in the CNS may be reflected in the biochemical composition of blood plasma. The combination of blood plasma and CSF provides more complete information about the disease. Both biofluids can be studied by use of NMR spectroscopy. It is then necessary to perform combined analysis of the two different datasets. Mid-level data fusion was therefore applied to blood plasma and CSF datasets. First, relevant information was extracted from each biofluid dataset by use of linear support vector machine recursive feature elimination. The selected variables from each dataset were concatenated for joint analysis by partial least squares discriminant analysis (PLS-DA). The combined metabolomics information from plasma and CSF enables more efficient and reliable discrimination of the onset of EAE. Second, we introduced hierarchical models fusion, in which previously developed PLS-DA models are hierarchically combined. We show that this approach enables neuroinflamed rats (even on the day of onset) to be distinguished from either healthy or peripherally inflamed rats. Moreover, progression of EAE can be investigated because the model separates the onset and peak of the disease. Figure  Graphical representation of Hierarchical Models Fusion applied to concatenated plasma and CSF datasets. Content Type Journal Article Category Original Paper Pages 1-13 DOI 10.1007/s00216-012-5871-4 Authors Agnieszka Smolinska, Institute for Molecules and Materials, Analytical Chemistry/ Biophysical Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands Joram M. Posma, Institute for Molecules and Materials, Analytical Chemistry/ Biophysical Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands Lionel Blanchet, Institute for Molecules and Materials, Analytical Chemistry/ Biophysical Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands Kirsten A. M. Ampt, Institute for Molecules and Materials, Analytical Chemistry/ Biophysical Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands Amos Attali, Abbott Healthcare Products B.V., 1381 CP Weesp, The Netherlands Tinka Tuinstra, Abbott Healthcare Products B.V., 1381 CP Weesp, The Netherlands Theo Luider, Department of Neurology, Erasmus University Medical Centre, Rotterdam, 3015 CE Rotterdam, The Netherlands Marek Doskocz, Spinnovation Analytical, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands Paul J. Michiels, Spinnovation Analytical, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands Frederic C. Girard, Spinnovation Analytical, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands Lutgarde M. C. Buydens, Institute for Molecules and Materials, Analytical Chemistry/ Biophysical Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands Sybren S. Wijmenga, Institute for Molecules and Materials, Analytical Chemistry/ Biophysical Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Chemotherapies feature a low success rate of about 25%, and therefore, the choice of the most effective cytostatic drug for the individual patient and monitoring the efficiency of an ongoing chemotherapy are important steps towards personalized therapy. Thereby, an objective method able to differentiate between treated and untreated cancer cells would be essential. In this study, we provide molecular insights into Docetaxel-induced effects in MCF-7 cells, as a model system for adenocarcinoma, by means of Raman microspectroscopy combined with powerful chemometric methods. The analysis of the Raman data is divided into two steps. In the first part, the morphology of cell organelles, e.g. the cell nucleus has been visualized by analysing the Raman spectra with k -means cluster analysis and artificial neural networks and compared to the histopathologic gold standard method hematoxylin and eosin staining. This comparison showed that Raman microscopy is capable of displaying the cell morphology; however, this is in contrast to hematoxylin and eosin staining label free and can therefore be applied potentially in vivo. Because Docetaxel is a drug acting within the cell nucleus, Raman spectra originating from the cell nucleus region were further investigated in a next step. Thereby we were able to differentiate treated from untreated MCF-7 cells and to quantify the cell–drug response by utilizing linear discriminant analysis models. Figure  Raman microspectroscopy in combination with powerful chemometric methods (e.g. artificial neural networks) indicates morphological (nucleus fragmentation) and spectral changes in Docetaxel treated breast cancer cells (MCF-7) in comparison to untreated cell samples Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-5887-9 Authors Katharina Hartmann, Institute of Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, 07743 Jena, Germany Melanie Becker-Putsche, Institute of Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, 07743 Jena, Germany Thomas Bocklitz, Institute of Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, 07743 Jena, Germany Katharina Pachmann, Department of Hematology and Oncology, Clinic for Internal Medicine II, University Hospital Jena, 07740 Jena, Germany Axel Niendorf, Pathologie Hamburg-West, Institut für diagnostische Histopathologie und Zytologie, Lornsenstraße 4, 22767 Hamburg, Germany Petra Rösch, Institute of Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, 07743 Jena, Germany Jürgen Popp, Institute of Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, 07743 Jena, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Botulinum neurotoxins (BoNTs) cause the disease botulism, which can be lethal if untreated. There are seven known serotypes of BoNT, A–G, defined by their response to antisera. Many serotypes are distinguished into differing subtypes based on amino acid sequence, and many subtypes are further differentiated into toxin variants. Previous work in our laboratory described the use of a proteomics approach to distinguish subtype BoNT/A1 from BoNT/A2 where BoNT identities were confirmed after searching data against a database containing protein sequences of all known BoNT/A subtypes. We now describe here a similar approach to differentiate subtypes BoNT/B1, /B2, /B3, /B4, and /B5. Additionally, to identify new subtypes or hitherto unpublished amino acid substitutions, we created an amino acid substitution database covering every possible amino acid change. We used this database to differentiate multiple toxin variants within subtypes of BoNT/B1 and B2. More importantly, with our amino acid substitution database, we were able to identify a novel BoNT/B subtype, designated here as BoNT/B7. These techniques allow for subtype and strain level identification of both known and unknown BoNT/B rapidly with no DNA required. Figure  Identification of an existing or new BoNT/B can be accomplished through MS/MS analysis of digestion fragments of the protein. Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s00216-012-5767-3 Authors Suzanne R. Kalb, Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, N.E., Atlanta, GA 30341, USA Jakub Baudys, Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, N.E., Atlanta, GA 30341, USA Jon C. Rees, Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, N.E., Atlanta, GA 30341, USA Theresa J. Smith, Integrated Toxicology, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA Leonard A. Smith, Office of the Chief Scientist, Medical Research and Materiel Command (MRMC), Fort Detrick, MD 21702, USA Charles H. Helma, Bioscience Division Los Alamos National Laboratory, Los Alamos, NM 87545, USA Karen Hill, Bioscience Division Los Alamos National Laboratory, Los Alamos, NM 87545, USA Skadi Kull, Robert Koch-Institut, Center for Biological Security, Microbial Toxins (ZBS3), 13353 Berlin, Germany Sebastian Kirchner, Robert Koch-Institut, Center for Biological Security, Microbial Toxins (ZBS3), 13353 Berlin, Germany Martin B. Dorner, Robert Koch-Institut, Center for Biological Security, Microbial Toxins (ZBS3), 13353 Berlin, Germany Brigitte G. Dorner, Robert Koch-Institut, Center for Biological Security, Microbial Toxins (ZBS3), 13353 Berlin, Germany James L. Pirkle, Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, N.E., Atlanta, GA 30341, USA John R. Barr, Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, N.E., Atlanta, GA 30341, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Two multi-analyte flow-through immunoassay formats for rapid detection of mycotoxins in a variety of food matrices (peanut cake, maize, and cassava flour) were developed and evaluated. The selected food matrices are typical staple foods and export products for most low-income communities around the world. The assay formats included gel-based and membrane-based flow-through assays and were based on the principle of indirect enzyme-linked immunosorbent assay. Using the same immunoreagents, the performance characteristics of both assays were compared. To the best of our knowledge, this is the first report on such a comparison. The gel-based format was developed to screen for ochratoxin A, fumonisin B 1 , deoxynivalenol, and zearalenone detection at cut-off values of 3, 1,250, 1,000, and 200 μg kg −1 , respectively, while the membrane-based format can be used to screen ochratoxin A, aflatoxin B 1, deoxynivalenol, and zearalenone at the following cut-offs: 3, 5, 700, and 175 μg kg −1 , respectively. The applicability of these assay formats was demonstrated by evaluating the performance characteristics of both tests through performing multiple experiments on different days. Both assays were further evaluated by analyzing naturally contaminated samples in the laboratory and also in the field under tropical conditions (Cameroon, West Africa). The false-negative rate with both formats was less than 5%, which is in good agreement with Commission Decision 2002/657/EC regarding the performance of analytical methods intended for screening purposes. Content Type Journal Article Category Original Paper Pages 1-14 DOI 10.1007/s00216-012-5803-3 Authors E. Njumbe Ediage, Laboratory of Food Analysis, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium J. Diana Di Mavungu, Laboratory of Food Analysis, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium I. Y. Goryacheva, Department of Common and Inorganic Chemistry, Chemistry Faculty, Saratov State University, Astrakhanskaya 83, 410012 Saratov, Russia C. Van Peteghem, Laboratory of Food Analysis, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium S. De Saeger, Laboratory of Food Analysis, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Three synthetic peptides, derived from the human potassium channel proteins Ether-a-go-go- related gene (HERG), KCNQ1, and KCNE1, were investigated by hydrogen deuterium exchange coupled with electron-transfer dissociation mass spectrometry at single residue resolution. Each amino acid residue in the first half of the HERG peptide incorporated deuterons with a higher rate than those in the second half of the peptide, consistent with the nuclear magnetic resonance structure of this peptide, with amino acids 1–10 being a flexible coil, whereas amino acids 11–24 are a stable amphipathic helix. The binding interface of KCNQ1 and KCNE1 was determined by comparing the difference of sequential fragment ions before and after binding. The residues determined to be involved in binding were consistent with a cysteine cross-linking study and confirmed by double mutant cycle analysis. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s00216-012-5857-2 Authors Jerri Chen, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA Ruth Angeletti, Laboratory of Macromolecular Analysis and Proteomics, Albert Einstein College of Medicine, Bronx, NY 10461, USA Thomas V. McDonald, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA Hui Xiao, Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The liquid chromatography–tandem mass spectrometry method (LC-MS/MS) was developed and validated to detect androgenic steroids: trenbolone, nortestosterone, boldenone, methylboldenone, testosterone, methyltestosterone, 17β-1-testosterone and their metabolites in bovine urine. Sample preparation before LC-MS/MS analysis involved an enzymatic hydrolysis with glucuronidase AS-HP, isolation of free hormones from urine on C 18 SPE column and purification of the extract using liquid–liquid extraction with n -pentane and SPE NH 2 column. For the chromatographic separation of steroids, the Poroshell 120-EC C18 column (150 × 2.1 mm, 2.7 μm) was used. Mass spectrometric measurement was achieved using the API 4000 triple quadrupole (QqQ) instrument with a TurboIon-Spray source operating in positive electrospray ionization mode. The procedure was validated according to the Decision 2002/657/EC. Recovery ranged from 76.5% to 118.9% for all examined compounds. The repeatability was below 20% and reproducibility did not exceed the 25%. The linearity was good for all analytes in the whole range of tested concentrations, as proved by the correlation coefficients greater than 0.99. The decision limit (CCα) ranged from 0.10 to 0.17 μg L −1 for all analytes, whereas the detection capability (CCβ) ranged from 0.17 to 0.29 μg L −1 . The application of an innovative Poroshell column allowed for very good chromatographic separation of steroids with a much shorter time of analysis. Figure  MRM chromatogram of 30 ng of androgenic steroids Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s00216-012-5859-0 Authors Barbara Wozniak, Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, Poland Iwona Matraszek-Zuchowska, Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, Poland Jan Zmudzki, Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, Poland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The Consultative committee for amount of substance-metrology in chemistry (CCQM)-K80 Key Comparison directly assessed the equivalence of many of the world’s higher-order value-assigned materials (HOVAMs) for creatinine in human serum. This 2009 international study compared the certified values and uncertainties of the materials using measurements made under repeatability conditions. The study evaluated 17 materials submitted by 6 national metrology institutes (NMIs). The creatinine quantity in these materials ranged from 3 mg/kg to 57 mg/kg (about 0.3 mg/dL to 6 mg/dL or 30 nmol/L to 500 nmol/L). All materials were stored and prepared according the specifications provided by the participating NMIs. Samples were processed and analyzed under repeatability conditions by one analyst using isotope-dilution liquid chromatography–mass spectrometry in two measurement campaigns. The certified values and repeatability measurements were compared using uncertainty-weighted generalized distance regression. The instrumental repeatability relative standard deviation was 1.2%. The measurement design required assessment of within-unit and between-campaign variability in addition to measurement repeatability. At a 95% level of confidence, the certified values for all 17 materials agreed to within their assigned uncertainties. CCQM-K80 demonstrated the metrological equivalence of the currently available HOVAMs for creatinine in human serum and of the creatinine measurement services provided by the participating NMIs. Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-5869-y Authors Johanna E. Camara, Analytical Chemistry Division, National Institute of Standards and Technology (NIST), 100 Bureau Drive, MS 8392, Gaithersburg, MD 20899-6392, USA Katrice A. Lippa, Analytical Chemistry Division, National Institute of Standards and Technology (NIST), 100 Bureau Drive, MS 8392, Gaithersburg, MD 20899-6392, USA David L. Duewer, Analytical Chemistry Division, National Institute of Standards and Technology (NIST), 100 Bureau Drive, MS 8392, Gaithersburg, MD 20899-6392, USA Hugo Gasca-Aragon, Analytical Chemistry Division, National Institute of Standards and Technology (NIST), 100 Bureau Drive, MS 8392, Gaithersburg, MD 20899-6392, USA Blaza Toman, Statistical Engineering Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899-8980, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    We investigated the ageing of amine-terminated self-assembled monolayers (amine-SAMs) on different silica substrates due to exposure to different ambient gases, pressures, and/or temperatures using time-of-flight secondary ion mass spectrometry (ToF-SIMS) with principal component analysis and complementary methods of surface analysis as X-ray photoelectron spectroscopy (XPS) and near edge X-ray absorption fine structure (NEXAFS). The goal of this study is to examine the durability of primary amine groups of amine-SAMs stored in a user laboratory prior to being used as supports for biomolecule immobilization and other applications. We prepared amine-SAMs on the native oxides of silicon wafers and glass slides using 3-aminopropyl triethoxysilane, by using optimized conditions such as anhydrous organic solvent and reaction time scale of hours to avoid multilayer growth. Selected commercial amine-SAM slides have been investigated, too. When the amine-SAMs are exposed to air, oxygen incorporation occurs, followed by formation of amide groups. The formation of oxygen species due to ageing was proved by ToF-SIMS, XPS, and NEXAFS findings such as CNO − secondary ion emission at m/z 42, observation of the N 1s HNC=O component peak at 400.2–400.3 eV in XPS, and, last but not least, by formation of a π*(HNC=O) resonance at 401 eV in the N K-edge X-ray absorption spectrum. It is concluded that the used multi-method approach comprising complementary ToF-SIMS, XPS, and NEXAFS analyses is well suited for a thorough study of chemical aspects of ageing phenomena of amine-SAM surfaces. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-5862-5 Authors Hyegeun Min, Surface and Thin Film Analysis WG, BAM Federal Institute for Materials Research and Testing, 12200 Berlin, Germany Pierre-Luc Girard-Lauriault, Surface and Thin Film Analysis WG, BAM Federal Institute for Materials Research and Testing, 12200 Berlin, Germany Thomas Gross, Surface and Thin Film Analysis WG, BAM Federal Institute for Materials Research and Testing, 12200 Berlin, Germany Andreas Lippitz, Surface and Thin Film Analysis WG, BAM Federal Institute for Materials Research and Testing, 12200 Berlin, Germany Paul Dietrich, Surface and Thin Film Analysis WG, BAM Federal Institute for Materials Research and Testing, 12200 Berlin, Germany Wolfgang E. S. Unger, Surface and Thin Film Analysis WG, BAM Federal Institute for Materials Research and Testing, 12200 Berlin, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    In this study, single and dual labeling of primary amino and thiol groups of target peptides is presented as a proof of concept. The proposed method allows flexible, independent and sequential labeling of the mentioned residues using lanthanides introduced via DOTA-complexes (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The efficiency of the method was optimized using cysteine-containing standard peptides and then applied to bovine serum albumin (BSA) and human serum albumin (HSA) to demonstrate qualitative and quantitative aspects of this strategy. For amino labeling, cysteinyl peptides were immobilized on Sepharose-6B resin and labeled with DOTA-NHS ester followed by metallation with lanthanides. Thiol labeling was carried out using lanthanide-containing metal-coded affinity tags (MeCAT) after elution of peptides from the resin. Complete dual labeling of the standard peptides was demonstrated by liquid chromatography electrospray ionization mass spectrometry, whereas more than 80 % of the detected peptides of BSA and HSA were completely dual-labeled. Parallel detection by LC coupled to inductively coupled plasma mass spectrometry (ICP-MS) delivered reliable quantitative information. Thus, the versatile lanthanide choice in both labeling steps allowed estimating primary amino and thiol stoichiometries for the studied samples using different lanthanides. On the other hand, enhancement of ICP-MS signal was achieved as expected when all positions were labeled with the same lanthanide. Finally, linear calibrations of the signal for most of the labeled peptides by standard additions of digested BSA showed a suitable behaviour for quantitative applications and demonstrated the pre-concentration capability of the employed resin. Figure    Content Type Journal Article Category Paper in Forefront Pages 1-13 DOI 10.1007/s00216-012-5910-1 Authors Ahmed H. El-Khatib, Department of Chemistry, Humboldt-Universitaet zu Berlin, Brook-Taylor Str. 2, 12489 Berlin, Germany Diego Esteban-Fernández, Department of Chemistry, Humboldt-Universitaet zu Berlin, Brook-Taylor Str. 2, 12489 Berlin, Germany Michael W. Linscheid, Department of Chemistry, Humboldt-Universitaet zu Berlin, Brook-Taylor Str. 2, 12489 Berlin, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Paper-based artworks are among the most valuable assets for transmission of knowledge. Historical paper is composed of different polysaccharides (e.g. cellulose), binders, and glues. During aging all of these components undergo several degradation processes, as a result of external and intrinsic causes, and these can compromise the state of conservation of the document. In this work, application of a new biotechnological strategy for paper artefact preservation is reported. By making use of innovative and non-invasive materials, for example appropriate hydrogels, in combination with selective electrochemical biosensors, it is possible to simultaneously verify the degradation condition of the paper artwork and then to efficiently clean it, while monitoring the process of removal of both pollution and degradation products. In this paper, we focus on specific examples in which such techniques have been applied to paper artworks and that illustrate the advantages and potential of this biotechnology compared with the traditional paper-cleaning methods currently in use. Figure  Scheme of cleaning treatment of old paper and determination of the interested analyte using Flow Injection Analysis system (FIA) with integrated electrochemical biosensor Content Type Journal Article Category Trends Pages 1-5 DOI 10.1007/s00216-012-5885-y Authors Laura Micheli, Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00173 Rome, Italy Claudia Mazzuca, Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00173 Rome, Italy Antonio Palleschi, Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00173 Rome, Italy Giuseppe Palleschi, Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00173 Rome, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Previously developed estrogen and androgen mammalian reporter gene assays (RGAs) were assessed for their potential use as a quantitative screening method in the detection of estrogenic and androgenic endocrine disruptors (EDs) in sport supplements. The validation of both RGAs coupled with dispersive solid phase extraction (dSPE) was performed in accordance with European Commission Decision EC/ 2002 /6579 for biological screening methods. Decision limits ( CCα ) and detection capabilities ( CCβ ) were established for both the estrogen and androgen RGAs. All samples were compliant with CCα and CCβ in both bioassays. Recovery rates were 96 % for 17β-estradiol and 115 % for dihydrotestosterone as obtained in their corresponding RGA. Both estrogens and androgens were stable in samples for more than 3 weeks, when stored at −20 °C. Specificity, good repeatability (coefficients of variation (CV), 12–25 %), reproducibility and robustness of both bioassays were also observed. Four different ED modes of action were determined for estrogens and androgens in 53 sport supplements, using the validated RGAs. This study revealed that 89 % of the investigated sport supplements contained estrogenic EDs and 51 % contained androgenic compounds. In conclusion, both bioassays are suitable for sport supplement screening of estrogenic and androgenic EDs. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-5905-y Authors Monika Plotan, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen’s University Belfast, Belfast, BT95AG Northern Ireland, UK Christopher T. Elliott, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen’s University Belfast, Belfast, BT95AG Northern Ireland, UK Michalina Oplatowska, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen’s University Belfast, Belfast, BT95AG Northern Ireland, UK Lisa Connolly, Institute of Agri-Food and Land Use, School of Biological Sciences, Queen’s University Belfast, Belfast, BT95AG Northern Ireland, UK Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Nanoparticles (NPs) of SiO 2 (15 nm) or Ag (20 – 40 nm) were dispersed in water, coffee and milk at several aqueous dilutions. The NPs dispersions concentrations were quantified with an ion beam technique: Particle-Induced X-ray Emission. Additional measurements in relation to the state of the NPs dispersions were done: particle size distribution by centrifuge liquid sedimentation and the extreme surface composition by X-ray photoelectron spectroscopy. The particle size distribution of SiO 2 and Ag NPs dispersions in water and Ag NPs in coffee remained mostly as primary particles with hydrodynamic diameters close to the reported pristine NPs diameter. SiO 2 NPs agglomerated in coffee. In milk, both NPs presented an adsorption with milk lipids. Extreme surface composition corroborated adsorption in milk and showed that SiO 2 agglomerates adsorb some coffee components. A linear tendency in the measurement of the concentration dilutions of all dispersions was measured, and a lack of media influence in the slope of each curve was found. Limits of detection with the current setup were estimated at 0.5 and 0.3 mg/ml for SiO 2 and Ag NPs, respectively. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s00216-012-5895-9 Authors Omar Lozano, Research Centre for the Physics of Matter and Radiation (PMR-LARN), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur (FUNDP), Rue de Bruxelles 61, 500 Namur, Belgium Jorge Mejia, Research Centre for the Physics of Matter and Radiation (PMR-LARN), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur (FUNDP), Rue de Bruxelles 61, 500 Namur, Belgium Tijani Tabarrant, Research Centre for the Physics of Matter and Radiation (PMR-LARN), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur (FUNDP), Rue de Bruxelles 61, 500 Namur, Belgium Bernard Masereel, Department of Pharmacy, Drug Design & Discovery Center (D3C), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur (FUNDP), Rue de Bruxelles 61, 500 Namur, Belgium Jean-Michel Dogné, Department of Pharmacy, Drug Design & Discovery Center (D3C), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur (FUNDP), Rue de Bruxelles 61, 500 Namur, Belgium Olivier Toussaint, Laboratory of Biochemistry and Cellular Biology (URBC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur (FUNDP), Rue de Bruxelles 61, 500 Namur, Belgium Stéphane Lucas, Research Centre for the Physics of Matter and Radiation (PMR-LARN), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur (FUNDP), Rue de Bruxelles 61, 500 Namur, Belgium Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The use of pharmaceuticals in livestock production is a potential source of surface water, groundwater and soil contamination. Possible impacts of antibiotics on the environment include toxicity and the emergence of antibiotic resistance. Monitoring programs are required to record the presence of these substances in the environment. A rapid, versatile and selective multi-method was developed and validated for screening 43 pharmaceutical and fungicides compounds, in surface and groundwater, in one single full-scan MS method, using benchtop U-HPLC–Exactive Orbitrap MS at 50,000 (FWHM) resolution. Detection was based on calculated exact masses and on retention time. Sample volume, pH conditions and solid-phase extraction (SPE) sample clean-up conditions were optimized. In the final method, 74 % of the compounds had recoveries higher than 80 %, 15 % of the compounds had recoveries between 60 % and 80 %, and 7 % of the compounds had recoveries between 40 % and 50 %. One of the compounds (itraconazole) had a recovery lower than 10 % and nystatin was not detected. The level of detection was 10 ng L −1 for 61 % of the compounds, 50 ng L −1 for 32 % and 100 ng L −1 for 5%. In-house validation, based on EU guidelines, proves that the detection capability CCβ is lower than 10 ng L −1 (for β error 5 %) for 37 % of the compounds, lower than 50 ng L −1 for 35 % of the compounds and lower than 100 ng L −1 for 14 % of compounds. This study demonstrates that the ultra-high resolution and reliable mass accuracy of Exactive Orbitrap MS permits the detection of pharmaceutical residues in a concentration range of 10–100 ng L −1 , applying a post target screening approach, in the multi-method conditions. Content Type Journal Article Category Original Paper Pages 1-15 DOI 10.1007/s00216-012-5888-8 Authors Carmen Lidia Chitescu, Faculty of Food Science and Engineering, “Dunarea de Jos” University of Galaţi, Str. Domnească 111, 800201 Galaţi, Romania Efraim Oosterink, RIKILT – Wageningen University and Research, P.O. Box 230, 6700 AE Wageningen, The Netherlands Jacob de Jong, RIKILT – Wageningen University and Research, P.O. Box 230, 6700 AE Wageningen, The Netherlands Alida Adriana Maria (Linda) Stolker, RIKILT – Wageningen University and Research, P.O. Box 230, 6700 AE Wageningen, The Netherlands Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: 16th Conference on Solid State Analysis Content Type Journal Article Category Editorial Pages 1-2 DOI 10.1007/s00216-012-5886-x Authors Gernot Friedbacher, Institute of Chemical Technologies and Analytics, Division of Instrumental Analytical Chemistry, Vienna University of Technology, Getreidemarkt 9/164-IAC, 1060 Vienna, Austria Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A method based on in-source collision-induced dissociation (ISCID) liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) and reverse target database search was developed and evaluated for drug screening and confirmation in analytical toxicology context. An established LC-TOFMS screening method, in which identification relies solely on protonated molecule accurate mass measurement, isotopic pattern fit, and retention time (RT), was completed to include 1–3 qualifier ions for each analyte in the database. The qualifier ions for 431 compounds were selected from the experimental ISCID spectra, and their molecular formulae were assigned by applying SmartFormula3D and MSFragmenter software. Three qualifier ions were assigned for 64.5%, two or three for 81.4%, one for 14.8%, and none for 3.7% of the compounds studied. Comparison between ISCID LC-TOFMS and LC-TOFMS with 25 authentic autopsy urine samples showed an improved confidence level with the ISCID method, as isomeric interferences were excluded in most cases. However, some false negative (FN) results were obtained at low concentration levels close to the reporting criteria. The cut-off concentration of the ISCID method was 10–100 ng/mL with 80% of the 49 representative compounds tested, and the level was approximately two times higher than that obtained by LC ion trap MS. The presented method enables simultaneous screening and confirmation whenever at least one qualifier ion is available, as applying an accurate mass precursor ion and one product ion surpasses the standard of four identification points that is required by the current EU protocol. Content Type Journal Article Category Original Paper Pages 1-14 DOI 10.1007/s00216-012-5889-7 Authors Ana de Castro, Institute of Forensic Sciences, Faculty of Medicine, San Francisco, s/n, 15782 Santiago de Compostela, Spain Merja Gergov, Hjelt Institute, Department of Forensic Medicine, University of Helsinki, PO Box 40, 00014 Helsinki, Finland Pekka Östman, Hjelt Institute, Department of Forensic Medicine, University of Helsinki, PO Box 40, 00014 Helsinki, Finland Ilkka Ojanperä, Hjelt Institute, Department of Forensic Medicine, University of Helsinki, PO Box 40, 00014 Helsinki, Finland Anna Pelander, Hjelt Institute, Department of Forensic Medicine, University of Helsinki, PO Box 40, 00014 Helsinki, Finland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A UPLC-ESI-MS/MS method has been developed and validated for the determination of larotaxel in beagle dog plasma. After addition of the internal standard, plasma samples were extracted by liquid–liquid extraction with methyl tert-butyl ether and separated on a 50 × 2.1 mm ACQUITY 1.7 μm C 18 column (Waters, USA), with acetonitrile and 5 mM ammonium acetate as mobile phase, within a runtime of 3.0 min. The analytes were detected without interference in Multiple Reaction Monitoring mode with positive electrospray ionization. The linear range was 2.5–5,000 ng/mL. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 9.3% and 10.2%, respectively, and the accuracy (relative error, RE, %) was less than 11.5%. The validated method was successfully applied to a pharmacokinetic study of larotaxel in beagle dogs after intravenous administration of larotaxel-loaded lipid microsphere with different doses of 0.4, 0.8, and 1.6 mg/kg. The area under the concentration–time curve and the peak concentration of larotaxel seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics. Figure  The concentration–time curves of larotaxel in beagle dog plasma after intravenous administration of LTX-LM at different doses of 0.4, 0.8, and 1.6 mg/kg Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s00216-012-5763-7 Authors Zhenzhen Liu, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Bo Zhang, School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, 110032 China Zhihong Liu, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Song Li, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Guofei Li, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Lulu Geng, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Xu Zhao, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Kaishun Bi, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Xing Tang, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Xiaohui Chen, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016 China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The use of Fourier transform infrared spectromicroscopy and mass spectrometry (MS) allowed us to characterize the composition of polar and non-polar binders present in sporadic wall paint fragments taken from Pompeii’s archaeological excavation. The analyses of the polar and non-polar binder components extracted from paint powder layer showed the presence of amino acids, sugars, and fatty acids but the absence of proteinaceous material. These results are consistent with a water tempera painting mixture composed of pigments, flours, gums, and oils and are in agreement with those obtained from a simulated wall paint sample made for mimicking an ancient “a secco” technique. Notably, for the first time, we report the capability to discriminate by tandem MS the presence of free amino acids in the paint layer. Content Type Journal Article Category Technical Note Pages 1-6 DOI 10.1007/s00216-012-5746-8 Authors Gaetano Corso, Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini, 5-80131 Napoli, Italy Monica Gelzo, Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini, 5-80131 Napoli, Italy Carmen Sanges, Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini, 5-80131 Napoli, Italy Angela Chambery, Dipartimento di Scienze per la Vita, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy Antimo Di Maro, Dipartimento di Scienze per la Vita, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy Valeria Severino, Dipartimento di Scienze per la Vita, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy Antonio Dello Russo, Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini, 5-80131 Napoli, Italy Ciro Piccioli, Accademia di Belle Arti di Napoli, Via Costantinopoli, 107-80138 Napoli, Italy Paolo Arcari, Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini, 5-80131 Napoli, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Mass spectrometry: Fifth meeting of the Spanish Society of Mass Spectrometry (SEEM) Content Type Journal Article Category Editorial Pages 1-2 DOI 10.1007/s00216-011-5690-z Authors José M. Vadillo, Department of Analytical Chemistry, University of Málaga, 29071 Málaga, Spain Damià Barceló, Catalan Institute for Water Research (ICRA), Parc Cientific i Tecnològic de la Universitat de Girona, Pic de Peguera 15, 17003 Girona, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The degradation of two β-blockers (atenolol and propranolol) and one β-receptor agonist (salbutamol) during water chlorination was investigated by liquid chromatography–mass spectrometry (LC-MS). An accurate-mass quadrupole time-of-flight system (QTOF) was used to follow the time course of the pharmaceuticals and also used in the identification of the by-products. The degradation kinetics of these drugs was investigated at different concentrations of chlorine, bromide and sample pH by means of a Box–Behnken experimental design. Depending on these factors, dissipation half-lives varied in the ranges 68–145 h for atenolol, 1.3–33 min for salbutamol and 42–8362 min for propranolol. Normally, an increase in chlorine dosage and pH resulted in faster degradation of these pharmaceuticals. Moreover, the presence of bromide in water samples also resulted in a faster transformation of atenolol at low chlorine doses. The use of an accurate-mass high-resolution LC-QTOF-MS system permitted the identification of a total of 14 by-products. The transformation pathway of β-blockers/agonists consisted mainly of halogenations, hydroxylations and dealkylations. Also, many of these by-products are stable, depending on the chlorination operational parameters employed. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-011-5707-7 Authors José Benito Quintana, Department of Analytical Chemistry, Nutrition and Food Science, IIAA—Institute for Food Analysis and Research, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain Rosario Rodil, Department of Analytical Chemistry, Nutrition and Food Science, IIAA—Institute for Food Analysis and Research, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain Rafael Cela, Department of Analytical Chemistry, Nutrition and Food Science, IIAA—Institute for Food Analysis and Research, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Triclosan, an antibacterial and antifungal agent, is widely used in household and personal care products, processed foods and food packaging, etc., and thus also released into the environment. Triclosan is acutely and chronically toxic to aquatic organisms and bioaccumulates in fish tissue. Here, we propose a new miniaturized triclosan extraction method for aqueous and fish roe samples, based on the use of a vortex mixer and an ultrasonic probe, respectively, and useful for triclosan determination by gas chromatography coupled to a micro electron capture detector. Different solvents for extraction and sorbents for clean-up purposes were tested. Multivariate optimization of the variables affecting ultrasonic extraction (ultrasound radiation amplitude, sonication time, sample temperature, and the ratio of sample amount and extracting volume) was carried out. Solvent extraction using ethyl acetate and further clean-up with mixed bed cartridges with two layers of Florisil® and Florisil® impregnated with 10% sulfuric acid only for fish roe samples was finally selected. Extraction efficiencies of up to 95% and 90%, and detection limits of 0.165 ng ml −1 and 2.7 ng g −1 for aqueous and fish roe samples were obtained, respectively. The optimized method was used in bioconcentration studies with zebrafish larvae ( Danio rerio ), as an alternative method to the Organization for Economic Cooperation and Development technical guideline 305. Bioconcentration values, BCF = 2,630 and 2,018 at exposure concentrations of 30 and 3 μg L −1 , respectively, were assessed. These results are in agreement with those reported in the literature, showing the feasibility of the method for estimation of toxicokinetic parameters and bioconcentration factors using zebrafish larvae instead of adult fishes, reducing considerable animal testing, as suggested by the European legislation. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-5713-4 Authors R. Gonzalo-Lumbreras, Department of Analytical Chemistry, Faculty of Chemistry, Universidad Complutense Madrid, Ciudad Universitaria, 28040 Madrid, Spain J. Sanz-Landaluze, Department of Analytical Chemistry, Faculty of Chemistry, Universidad Complutense Madrid, Ciudad Universitaria, 28040 Madrid, Spain J. Guinea, Zf BioLabs, Ronda de Valdecarrizo 41º B. 28760. Tres Cantos, Madrid, Spain C. Cámara, Department of Analytical Chemistry, Faculty of Chemistry, Universidad Complutense Madrid, Ciudad Universitaria, 28040 Madrid, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Traditional activity-guided fractionation of natural products is a time-consuming, labor intensive, and expensive strategy, which cannot compete with high-throughput and rapid screening of natural products. Therefore, more efficient approaches are necessary for searching active compounds from natural products. Three main methods based on high-performance liquid chromatography (HPLC) analysis combined with 2,2′-diphenyl-1-picrylhydrazyl (DPPH) assay, DPPH spiking HPLC analysis, on-line post-column HPLC-DPPH analysis, and HPLC-based DPPH activity profiling, were then developed for the rapid screening of antioxidants from complex mixtures. In the present study, a comparative study of these three methods has been conducted to identify antioxidants from an ethyl acetate fraction of Pueraria lobata flowers. The parameters in HPLC analysis and DPPH assay were optimized. The results indicated that all three methods could achieve similar information with regard to antioxidants, without the need for preparative isolation techniques. However, there were differences in instrumental set-up, sensitivity, and efficiency. DPPH spiking HPLC analysis seemed to be more sensitive and effective with simpler instrumental set-up and easier operation, which could also detect the total antioxidant capacity of color complexes. Eighteen antioxidants were tentatively screened and identified from P. lobata flowers by DPPH spiking HPLC-MS/MS. Among them, ten compounds including one new compound were first isolated from P. lobata flowers, and the DPPH radical scavenging activity of the new compound was reported for the first time. Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s00216-012-5722-3 Authors Yu-Ping Zhang, State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083 China Shu-Yun Shi, State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083 China Xiang Xiong, State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083 China Xiao-Qing Chen, School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083 China Mi-Jun Peng, Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Zhangjiajie, 427000 China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography–mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography–mass spectrometry to liquid chromatography–mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High-resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier-transform mass spectrometry. Both techniques enable a range of different drug-screening strategies that essentially rely on measuring a compound’s or a fragment’s mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology. Content Type Journal Article Category Review Pages 1-18 DOI 10.1007/s00216-012-5726-z Authors Ilkka Ojanperä, Hjelt Institute, Department of Forensic Medicine, Forensic Toxicology Division, University of Helsinki, P.O. Box 40, 00014 Helsinki, Finland Marjo Kolmonen, Hjelt Institute, Department of Forensic Medicine, Forensic Toxicology Division, University of Helsinki, P.O. Box 40, 00014 Helsinki, Finland Anna Pelander, Hjelt Institute, Department of Forensic Medicine, Forensic Toxicology Division, University of Helsinki, P.O. Box 40, 00014 Helsinki, Finland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    This study describes a rapid and sensitive analytical method for the determination of amino acids in foods and drinks. The method entailed dilution or extraction of amino acids from foods using the mixture of acetonitrile and 0.1% aqueous formic acid (50:50, v/v ). Chromatographic separation of underivatized amino acids was performed using a hydrophilic interaction liquid chromatography within a runtime of 6 min. Both hydrophobicity and charge of the side chain played important roles on the elution order of amino acids under the chromatographic conditions. High-resolution mass spectrometry allowed qualitative and quantitative detection of amino acids in complex food matrices. Its response was found linear over a concentration range of 0.25–10 μg/ml. The method could be successfully applied to various foods and drinks to profile individual amino acids. Mean percentage recoveries of amino acids from different matrices were 88.5% or higher with residual standard deviation of less than 5.0%. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s00216-012-5779-z Authors Vural Gökmen, Food Engineering Department, Hacettepe University, 06800 Beytepe, Ankara, Turkey Arda Serpen, Food Research Center, Hacettepe University, 06800 Beytepe, Ankara, Turkey Burçe Ataç Mogol, Food Engineering Department, Hacettepe University, 06800 Beytepe, Ankara, Turkey Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    In the work discussed in this paper, the effect of a high surface-to-volume ratio of a microfluidic detection cell on fluorescence quenching was studied. It was found that modification of the geometry of a microchannel can provide a wider linear range. This is a phenomenon which should be taken into consideration when microfluidic systems with fluorescence detection are developed. The dependence of the linear range for fluorescein on the surface-to-volume ratio was determined. Both fluorescence inner-filter effects and concentration self-quenching were taken into consideration. It was found that inner-filter effects have little effect on the extent of the linear range on the microscale. Figure  Dependence of the linear range on surface-to-volume ratio in microfluidic detection. Content Type Journal Article Category Short Communication Pages 1-5 DOI 10.1007/s00216-012-5770-8 Authors Radoslaw Kwapiszewski, Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland Karina Ziolkowska, Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland Kamil Zukowski, Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland Michal Chudy, Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland Artur Dybko, Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland Zbigniew Brzozka, Department of Microbioanalytics, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Erratum to: Microcantilevers and organic transistors: two promising classes of label-free biosensing devices which can be integrated in electronic circuits Content Type Journal Article Category Erratum Pages 1-1 DOI 10.1007/s00216-012-5775-3 Authors Serafina Cotrone, Department of Chemistry, University of Bari, 70126 Bari, Italy Damiana Cafagna, Department of Chemistry, University of Bari, 70126 Bari, Italy Stefania Cometa, Department of Chemistry and Industrial Chemistry, Pisa University, 56126 Pisa, Italy Elvira De Giglio, Department of Chemistry, University of Bari, 70126 Bari, Italy Maria Magliulo, Department of Chemistry, University of Bari, 70126 Bari, Italy Luisa Torsi, Department of Chemistry, University of Bari, 70126 Bari, Italy Luigia Sabbatini, Department of Chemistry, University of Bari, 70126 Bari, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    This paper describes the development of a novel on-line biosensor based on a fluorescently labeled human calmodulin (CaM), h CaM M124C- mBBr , immobilized on controlled-pore glass (CPG), for the analysis of trifluoroperazine (TFP); a phenothiazine drug in human urine samples. The device was automated by packing h CaM M124C- mBBr -CPG in a continuous-flow microcell connected to a monitoring system, composed of a bifurcated optical fiber coupled to a spectrofluorometer. Operating parameters of the on-line biosensor (flow rate, sample injection volume, and carrier solution and buffer pH) were studied and optimized. Under the optimal conditions, the biosensor provides a detection and a quantification limit of 0.24 and 0.52 μg mL −1 , respectively, and a dynamic range from 0.52 to 61.05 μg mL −1 TFP ( n  = 5, correlation coefficient 0.998). The response time ( t 100 ) was shorter than 42 s (recovery time 〈4.5 min) and reproducibility and repeatability of the TFP measurements, within the linear response range, were lower than 1.4 and 2.7%, respectively. The device was successfully applied to the analysis of TFP in spiked human urine samples with recoveries ranging between 97 and 101% and with RSDs lower than 5.9%. Figure  Artistic depiction of the on-line biosensor working principle for trifluoroperazine analysis in urine samples. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s00216-011-5701-0 Authors Martin González-Andrade, Departamento de Química Analítica, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain Elena Benito-Peña, Departamento de Química Analítica, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain Rachel Mata, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Federal District, 04510 Mexico Maria C. Moreno-Bondi, Departamento de Química Analítica, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A biomimetic sensor has been developed, that allows for quantification of autoantibodies related to the antiphospholipid syndrome (APS). Autoantibodies directed against the β 2 -glycoprotein-I (β 2 GP-I) are known as the best markers for diagnosis of APS, however, detection of such antibodies is still a challenge. The epitopes of β 2 GP-I are exposed upon binding to negatively charged membranes. The surface of the sensor chips was therefore modified with such type of membranes, on which β 2 GP-I molecules were subsequently immobilized as recognition elements. Using the label-free method, reflectometric interference spectroscopy, it was possible to quantify anti-β 2 GP-I antibodies and to calibrate the sensor chip in buffer. A mild regeneration procedure allows for many consecutive measurements without stripping off the membrane in between. Content Type Journal Article Category Short Communication Pages 1-5 DOI 10.1007/s00216-012-5831-z Authors Urs Hilbig, Institute of Physical and Theoretical Chemistry (IPTC), Eberhard Karls University Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany Oliver Bleher, Institute of Physical and Theoretical Chemistry (IPTC), Eberhard Karls University Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany Alexander Le Blanc, Institute of Physical and Theoretical Chemistry (IPTC), Eberhard Karls University Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany Günter Gauglitz, Institute of Physical and Theoretical Chemistry (IPTC), Eberhard Karls University Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Four disulfide-reducing agents, dithiothreitol (DTT), 2,3-dimercaptopropanesulfonate (DMPS), and the newly tested 2-mercaptoethanesulfonate (MESNA) and Tris(hydroxypropyl)phosphine (THP), were investigated in detail for release of sulfur amino acids in human plasma. After protein precipitation with trichloroacetic acid (TCA), the plasma supernatant was treated with methyl, ethyl, or propyl chloroformate via the well-proven derivatization–extraction technique and the products were subjected to gas chromatographic–mass spectrometric (GC–MS) analysis. All the tested agents proved to be rapid and effective reducing agents for the assay of plasma thiols. When compared with DTT, the novel reducing agents DMPS, MESNA, and THP provided much cleaner extracts and improved analytical performance. Quantification of homocysteine, cysteine, and methionine was performed using their deuterated analogues, whereas other analytes were quantified by means of 4-chlorophenylalanine. Precise and reliable assay of all examined analytes was achieved, irrespective of the chloroformate reagent used. Average relative standard deviations at each analyte level were ≤6%, quantification limits were 0.1–0.2 μmol L −1 , recoveries were 94–121%, and linearity was over three orders of magnitude ( r 2 equal to 0.997–0.998). Validation performed with the THP agent and propyl chloroformate derivatization demonstrated the robustness and reliability of this simple sample-preparation methodology. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-5727-y Authors Zdeněk Švagera, Institute of Clinical Biochemistry, Faculty Hospital Ostrava, 17, Listopadu 1790, 708 52 Ostrava, Czech Republic Dagmar Hanzlíková, Institute of Clinical Biochemistry, Faculty Hospital Ostrava, 17, Listopadu 1790, 708 52 Ostrava, Czech Republic Petr Šimek, Biology Centre, Laboratory of Analytical Biochemistry, Branišovská 31, 370 05 České Budějovice, Czech Republic Petr Hušek, Institute of Clinical Biochemistry, Faculty Hospital Ostrava, 17, Listopadu 1790, 708 52 Ostrava, Czech Republic Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Patient-specific sequential epitopes were identified by peptide chip analysis using 15mer peptides immobilized on glass slides that covered the topoisomerase IIa protein with a frameshift of five amino acids. Binding specificities of serum antibodies against sequential epitopes were confirmed as being mono-specific by peptide chip re-analysis of epitope-affinity-purified antibody pools. These results demonstrate that serum samples from colon carcinoma patients contain antibodies against sequential epitopes from the topoisomerase IIa antigen. Interactions of patients’ antibodies with sequential epitopes displayed by peptides on glass surfaces may thus mirror disease-specific immune situations. Consequently, these data suggest epitope–antibody reactivities on peptide chips as potential diagnostic readouts of individual immune response characteristics, especially because monospecific antibodies can be interrogated. Subsequently, the clonality of the antibodies present in the mono-specific antibody pools was characterized by 2D gel electrophoresis. This analysis suggested that the affinity-purified antibodies were oligoclonal. Similarly to large-scale screening approaches for specific antigen–antibody interactions in order to improve disease diagnostic, we suggest that “protein-wide” screening for specific epitope–paratope interactions may help to develop novel assays for monitoring of personalized therapies, since individual properties of antigen–antibody interactions remain distinguishable. Figure    Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s00216-012-5781-5 Authors Michael Linnebacher, Department of General Surgery, Molecular Oncology and Immunotherapy, Medical Faculty, University of Rostock, 18055 Rostock, Germany Peter Lorenz, Institute of Immunology, Medical Faculty, University of Rostock, 18055 Rostock, Germany Cornelia Koy, Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, 18055 Rostock, Germany Annika Jahnke, Department of General Surgery, Molecular Oncology and Immunotherapy, Medical Faculty, University of Rostock, 18055 Rostock, Germany Nadine Born, Institute of Immunology, Medical Faculty, University of Rostock, 18055 Rostock, Germany Felix Steinbeck, Institute of Immunology, Medical Faculty, University of Rostock, 18055 Rostock, Germany Johannes Wollbold, Institute of Immunology, Medical Faculty, University of Rostock, 18055 Rostock, Germany Tobias Latzkow, IndyMED GmbH, 18055 Rostock, Germany Hans-Jürgen Thiesen, Institute of Immunology, Medical Faculty, University of Rostock, 18055 Rostock, Germany Michael O. Glocker, Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, 18055 Rostock, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Lipids in skeletal muscle play a fundamental role both in normal muscle metabolism and in disease states. Skeletal muscle lipid accumulation is associated with several chronic metabolic disorders, including obesity, insulin resistance, and type 2 diabetes. However, it is poorly understood whether the lipid composition of skeletal muscle changes by contraction, due to the complexity of lipid molecular species. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to investigate changes in skeletal muscle lipid composition induced by contraction. We successfully observed the reduction of diacylglycerol and triacylglycerol, which are generally associated with muscle contraction. Interestingly, we found the accumulation of some saturated and mono-unsaturated fatty acids and poly-unsaturated fatty acids containing phosphatidylcholine in contracted muscles. Moreover, the distributions of several types of lipid were changed by contraction. Our results show that changes in the lipid amount, lipid composition, and energy metabolic activity can be evaluated in each local spot of cells and tissues at the same time using MALDI-IMS. In conclusion, MALDI-IMS is a powerful tool for studying lipid changes associated with contractions. Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-5809-x Authors Naoko Goto-Inoue, Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1, Minami-Osawa, Hachioji, Tokyo, 192-0397 Japan Yasuko Manabe, Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1, Minami-Osawa, Hachioji, Tokyo, 192-0397 Japan Shouta Miyatake, Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1, Minami-Osawa, Hachioji, Tokyo, 192-0397 Japan Shinya Ogino, Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1, Minami-Osawa, Hachioji, Tokyo, 192-0397 Japan Ai Morishita, Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1, Minami-Osawa, Hachioji, Tokyo, 192-0397 Japan Takahiro Hayasaka, Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan Noritaka Masaki, Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan Mitsutoshi Setou, Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan Nobuharu L. Fujii, Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1, Minami-Osawa, Hachioji, Tokyo, 192-0397 Japan Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A new high-performance liquid chromatographic method with triple quadrupole mass spectrometry detection was developed and validated for the quantification of zopiclone enantiomers in rat brain samples. Zopiclone enantiomers were resolved on a CHIRALPAK AD column with a mobile phase consisting of acetonitrile/ethanol/methanol (60:20:20, v/v/v ) at a flow rate of 1.3 mL min -1 . Moclobemide was used as internal standard. The sample treatment procedure was carried out employing solid-phase extraction, yielding mean absolute recoveries of 89.6 and 91.7 % for each zopiclone enantiomer. The validated method showed linearity in the range of 0.29–344.8 ng g −1 , with quantification limits of 0.29 ng g −1 for both enantiomers. Precision and accuracy were within acceptable levels of confidence (〈15 %). The method was applied in a pilot study of zopiclone kinetic disposition in rats. It could be observed that the levels of (+)-( S )-zopiclone were always higher than those of (-)-( R )-zopiclone, confirming the stereoselective disposition of zopiclone. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s00216-012-6487-4 Authors Milena Araújo Tonon, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14040-903 SP, Brazil Valquíria A. P. Jabor, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14040-903 SP, Brazil Pierina Sueli Bonato, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14040-903 SP, Brazil Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    For many analytical purposes, direct laser ionization of liquids is desirable. Several studies on supported droplets, free liquid jets, and ballistically dispensed microdroplets have been conducted, yet detailed knowledge of the underlying mechanistics in ion formation is still missing. This contribution introduces a simple combination of IR-MALDI mass spectrometry and an acoustical levitation device for contactless confinement of the liquid sample. The homebuilt ultrasonic levitator supports droplets of several millimeters in diameter. These droplets are vaporized by a carbon dioxide laser in the vicinity of the atmospheric pressure interface of a time of flight mass spectrometer. The evaporation process is studied by high repetition rate shadowgraphy experiments elucidating the ballistic evaporation of the sample and revealing strong confinement of the vapor by the ultrasonic field of the trap. Finally, typical mass spectra for pure glycerol/water matrix and lysine as an analyte are presented with and without the addition of trifluoracetic acid, and the ionization mechanism is briefly discussed. The technique is a promising candidate for a reproducible mass spectrometric detection scheme for the field of microfluidics. Figure  CO 2 laser evaporation of an acoustic levitated droplet followed by time of flight mass analysis Content Type Journal Article Category Original Paper Pages 1-6 DOI 10.1007/s00216-012-6500-y Authors Arne Stindt, BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, Germany Merwe Albrecht, BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, Germany Ulrich Panne, BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, Germany Jens Riedel, BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The hydrogen isotope ratio (HIR) of body water and, therefore, of all endogenously synthesized compounds in humans, is mainly affected by the HIR of ingested drinking water. As a consequence, the entire organism and all of its synthesized substrates will reflect alterations in the isotope ratio of drinking water, which depends on the duration of exposure. To investigate the effect of this change on endogenous urinary steroids relevant to doping-control analysis the hydrogen isotope composition of potable water was suddenly enriched from -50 to 200 ‰ and maintained at this level for two weeks for two individuals. The steroids under investigation were 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 5α-androstane-3α,17β-diol, and 5β-androstane-3α,17β-diol (excreted as glucuronides) and ETIO, ANDRO and 3β-hydroxyandrost-5-en-17-one (excreted as sulfates). The HIR of body water was estimated by determination of the HIR of total native urine, to trace the induced changes. The hydrogen in steroids is partly derived from the total amount of body water and cholesterol-enrichment could be calculated by use of these data. Although the sum of changes in the isotopic composition of body water was 150 ‰, shifts of approximately 30 ‰ were observed for urinary steroids. Parallel enrichment in their HIR was observed for most of the steroids, and none of the differences between the HIR of individual steroids was elevated beyond recently established thresholds. This finding is important to sports drug testing because it supports the intended use of this novel and complementary methodology even in cases where athletes have drunk water of different HIR, a plausible and, presumably, inevitable scenario while traveling. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-6504-7 Authors Thomas Piper, Swiss Laboratory for Doping Analysis, University Center of Legal Medicine, Geneva and Lausanne, Centre Hospitalier Universitaire Vaudois and University Lausanne, Ch. des Croisettes 22, 1066 Epalinges, Switzerland Karoline Degenhardt, Swiss Laboratory for Doping Analysis, University Center of Legal Medicine, Geneva and Lausanne, Centre Hospitalier Universitaire Vaudois and University Lausanne, Ch. des Croisettes 22, 1066 Epalinges, Switzerland Eugen Federherr, Elementar Analysensysteme GmbH, Donaustr. 7, 63452 Hanau, Germany Andreas Thomas, German Sport University Cologne, Center for Preventive Doping Research—Institute of Biochemistry, Am Sportpark Müngersdorf 6, 50933 Köln, Germany Mario Thevis, German Sport University Cologne, Center for Preventive Doping Research—Institute of Biochemistry, Am Sportpark Müngersdorf 6, 50933 Köln, Germany Martial Saugy, Swiss Laboratory for Doping Analysis, University Center of Legal Medicine, Geneva and Lausanne, Centre Hospitalier Universitaire Vaudois and University Lausanne, Ch. des Croisettes 22, 1066 Epalinges, Switzerland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Phytohormones act at relatively low concentrations as major regulatory factors of plant growth and development, and cross talk of phytohormones is currently of great interest throughout the plant science community. To meet this demand, a method that is capable of simultaneously analyzing diverse plant hormones is essential. This paper introduces a high-performance liquid chromatographic separation technique coupled with sensitive and selective ion trap mass spectrometry to simultaneously determine 24 or more acidic and alkaline phytohormones, including auxin, cis - and trans -abscisic acid, 11 cytokinins, and 10 gibberellins, in a single injection of sample. A binary solid-phase extraction using Oasis MCX cartridges for cations and Oasis MAX cartridges for anions was used to prepurify more than 24 acidic and alkaline phytohormones from a single plant extract. The method showed good linearity for all 24 phytohormones with R 2 values ranging from 0.9903 to 0.9997. Limits of detection for most of the phytohormones were in the femtomole range with some extending into the sub-femtomole range. This method was applied to hundreds of plant samples comprising different tissues from various plants, including herbaceous, woody climbing, and woody plants to demonstrate feasibility and to validate the methodology. Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s00216-012-6509-2 Authors Shichang Liu, College of Life Sciences and Biotechnology, Beijing Forestry University, Beijing, 100083 China Weiqi Chen, College of Life Sciences and Biotechnology, Beijing Forestry University, Beijing, 100083 China Long Qu, College of Life Sciences and Biotechnology, Beijing Forestry University, Beijing, 100083 China Ying Gai, College of Life Sciences and Biotechnology, Beijing Forestry University, Beijing, 100083 China Xiangning Jiang, College of Life Sciences and Biotechnology, Beijing Forestry University, Beijing, 100083 China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Graphene-nanosheet-based highly porous magnetite nanocomposites (GN-HPMNs) have been prepared using a simple solvothermal method and used as an immobilization matrix for the fabrication of a solid-state electrochemiluminescence (ECL) sensor on paper-based chips. Highly porous Fe 3 O 4 nanocrystal clusters were coated with acrylate and wrapped tightly on the skeleton of graphene nanosheets. The structures and sizes of the GN-HPMNs could be tuned by varying the proportions of the solvents ethylene glycol and diethylene glycol. Then, the relatively highly porous ones with an average diameter of about 65 nm were combined with Nafion to form composite films on an electrode surface for immobilization of Ru(bpy) 3 2+ (bpy is 2,2′-bipyridine). Because of their porosity, negatively charged surface, and cooperative characteristics of magnetic nanomaterials and graphene, under an external magnetic field, the GN-HPMNs ensured effective immobilization, excellent electron transfer, and long-term stability of Ru(bpy) 3 2+ in the composite film. The sensor developed exhibited excellent reproducibility with a relative standard deviation of 0.65 % for 30 continuous cycles. It was found to be much more favorable for detecting compounds containing tertiary amino groups and DNAs with guanine and adenine. A detection limit (signal-to-noise ratio of 3) of 5.0 nM was obtained for tripropylamine. As an application example, 0.5 nM single-nucleotide mismatch could be detected. This was the first attempt to introduce magnetic nanomaterials and an external magnetic field into paper-based chips. The sensor developed has the advantages of high sensitivity, good stability, and wide potential applicability as well as simplicity, low cost, and good disposability. Figure  Schematic diagram of using graphene-nanosheet-based highly porous magnetite nanocomposites for fabrication of a solid-state electrochemiluminescence sensor on paper-based chips and application example of the developed sensor for single-nucleotide mismatch discrimination Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s00216-012-6510-9 Authors Yuanhong Xu, State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China Zhaozi Lv, State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China Yong Xia, State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China Yanchao Han, State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China Baohua Lou, State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China Erkang Wang, State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Purpose   To investigate whether general practitioners, hospital physicians and specialized practitioners in psychiatry have similar preferences for initiating treatment with expensive serotonin-specific reuptake inhibitors (SSRIs). Methods   All first-time prescriptions for the SSRIs escitalopram, citalopram and sertraline reported to the Danish National Register of Medicinal Product Statistics from April 1, 2009 until March 31, 2010 were analysed with regard to treatment naivety and type of prescriber. A prescription was considered as first time if the patient had not received a prescription for the same drug within the last 2 years. Patients who had not received a prescription for an antidepressant within 6 months prior to the date of redemption were classified as treatment-naïve. Results   We included 82,702 first-time prescriptions, 65,313 (79 %) of which were for treatment-naïve patients. Of the treatment-naïve patients, 19 % were initially prescribed escitalopram. Hospital physicians prescribed escitalopram to 34 % of their treatment-naïve patients, while practitioners specialized in psychiatry prescribed it to 25 %, and general practitioners prescribed it to 17 %. General practitioners, however, were responsible for initiating 87 % of all treatment-naïve patients. Conclusion   The most expensive SSRI, escitalopram, is prescribed as first choice to one in five patients receiving their first antidepressant of escitalopram, citalopram or sertraline. General practitioners made the bulk of all first-time SSRI prescriptions to treatment-naïve patients. Content Type Journal Article Category Pharmacoepidemiology and Prescription Pages 1-5 DOI 10.1007/s00228-012-1447-7 Authors Karen Killerup Poulsen, Faculty of Health and Medicines Sciences, University of Copenhagen, Copenhagen, Denmark Dorte Glintborg, Institute for Rational Pharmacotherapy, Copenhagen, Denmark Søren Ilsøe Moreno, Institute for Rational Pharmacotherapy, Copenhagen, Denmark Steffen Thirstrup, Danish Health and Medicines Authority, Copenhagen, Denmark Lise Aagaard, Institute of Public Health, Clinical Pharmacology, Faculty of Health Sciences, University of Southern Denmark, JB Winsløws Vej 19, 5000 Odense C, Denmark Stig Ejdrup Andersen, Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description:    Histone acetyltransferases (HATs) catalyze the acetylation of specific lysine residues in histone and nonhistone proteins. Recent studies showed that acetylation is widely distributed among cellular proteins, suggestive of diverse functions of HATs in cellular pathways. Nevertheless, currently available assays for HAT activity study are still quite limited. Here, we evaluated a series of thiol-sensitive fluorogenic compounds for the detection of the enzymatic activities of different HAT proteins. Upon conjugation to the thiol group of HSCoA, these molecules gain enhanced quantum yields and strong fluorescence, permitting facile quantitation of HAT activities. We investigated and compared the assay performances of these fluorogenic compounds for their capability as HAT activity reporters, including kinetics of reaction with HSCoA, influence on HAT activity, and fluorescence amplification factors. Our data suggest that CPM and coumarin maleic acid ester are excellent HAT probes owing to their fast reaction kinetics and dramatic fluorescence enhancement during the HAT reaction. Further, the microtiter plate measurements show that this fluorescent approach is robust and well suited for adaption to high-throughput screening of small molecule inhibitors of HATs, highlighting the value of this assay strategy in new drug discovery. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-6522-5 Authors Tielong Gao, Department of Chemistry, Georgia State University, PO Box 4098, Atlanta, GA 30302, USA Chao Yang, Department of Chemistry, Georgia State University, PO Box 4098, Atlanta, GA 30302, USA Yujun George Zheng, Department of Chemistry, Georgia State University, PO Box 4098, Atlanta, GA 30302, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Letter to the Editor regarding “Quantification of Paraquat, MPTP, and MPP+ in brain tissue using microwave-assisted solvent extraction (MASE) and high-performance liquid chromatography–mass spectrometry” Content Type Journal Article Category Letter to the Editor Pages 1-1 DOI 10.1007/s00216-012-6503-8 Authors Brian Buckley, Rutgers University–EOHSI, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The uncertainties of stable isotope results depend not only on the technical aspects of measurements, but also on how raw data are normalized to one of the international isotope scales. The inconsistency in the normalization methods used and in the selection of standards may lead to substantial differences in the results obtained. Therefore, unification of the data processing protocols employed is highly desirable. The best performing methods are two-point or multipoint normalization methods based on linear regression. Linear regression is most robust when based on standards that cover the entire range of δ values typically observed in nature, regardless of the δ values of the samples analysed. The uncertainty can be reduced by 50 % if measurements of two different standards are performed four times, or measurements of four standards are performed twice, with each batch of samples. Chemical matrix matching between standards and samples seems to be critical for δ 18 O of nitrate or δ 2 H of hair samples (thermal conversion/elemental analyser), for example; however, it is not necessarily always critical for all types of samples and techniques (e.g. not for most δ 15 N and δ 13 C elemental analyser analyses). To ensure that all published data can be recalculated, if δ values of standards or the isotope scales are to be updated, the details of the normalization technique and the δ values of the standards used should always be clearly reported. Content Type Journal Article Category Review Pages 1-9 DOI 10.1007/s00216-012-6517-2 Authors Grzegorz Skrzypek, West Australian Biogeochemistry Centre, School of Plant Biology, The University of Western Australia, M090, 35 Stirling Highway, Crawley, WA 6009, Australia Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Bringing pharmacogenetics to the bedside Content Type Journal Article Category Letter to the Editors Pages 1-2 DOI 10.1007/s00228-012-1444-x Authors Ankur Gupta, Department of Cardiology, Hartford Hospital, Cardiology, 80 Seymour Street, Hartford, 06106, CT, USA Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description: Purpose   It is recognised that paediatric prescribing errors are prevalent, and that most are made by junior doctors; however, detecting errors in order to demonstrate actual error rates can be difficult. There is evidence to suggest that dosing errors are the most common type of prescribing error in practice, but there has been little research on whether prescribing assessments are an effective reflection of actual practice.This article aims to determine if prescribing error types in a paediatric prescribing competency assessment reflects error types seen in actual practice. Methods   This study was conducted in Royal Manchester Children’s Hospital (RMCH) and the participants were junior doctors working at RMCH in 2010-2011. The intervention was a prescribing competency assessment package at RMCH.The main outcome measurement was the category and rate of prescribing errors. Results were taken from the junior doctors’ prescribing competency assessment. The assessment papers were analysed for errors and the errors were then broken down into pre-defined categories. Results   Rates of prescribing errors in the competency assessment are higher than published results shown in practice (23.1 %). The most common type of prescribing error (incorrect calculation of dose) reflects results seen in actual practice. Conclusion   The types of prescribing errors made in the competency assessment are reflective of errors made in actual practice. Prescribing teaching can be tailored according to the types of errors noted; and the prescribing competency package as a whole can be used to educate junior doctors on good prescribing practice and reduce prescribing errors. Content Type Journal Article Category Pharmacoepidemiology and Prescription Pages 1-4 DOI 10.1007/s00228-012-1440-1 Authors Tessa Davis, Medical Leadership Programme, North Western Deanery, Manchester, UK Hong Thoong, Royal Manchester Children’s Hospital, Pharmacy Department, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Anna Kelsey, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Guy Makin, Institute of Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description: Background/aim   Timed interval cerebrospinal fluid (CSF) sampling by indwelling catheterization can be a valuable corroborative tool for the pharmacokinetic and pharmacodynamic assessment of drugs. CSF sampling in studies on drug candidates for Alzheimer’s disease have been conducted in evaluations of the biomarkers acetylcholine (ACh), tau proteins, amyloid precursor protein and beta-amyloid fragments. The primary aim of this study was to study the feasibility and the burden on the healthy volunteers of serial CSF sampling within the contract research organization environment in order to establish a standardized research tool for future drug development studies. Materials and methods   This study is a validation study in healthy subjects: eight healthy male subjects aged 55–75 years were enrolled. After eligibility had been confirmed, the subjects were admitted to the clinical pharmacology unit 2 days before starting the CSF sampling procedure. Hydration by drip infusion of 2 L saline was performed for 24 h before starting the CSF sampling procedure, and for antithrombotic purposes, Fraxiparine (nadroparine calcium) was given 12 and 36 h after intradural catheterization. CSF catheterization was performed by board-certified anesthesiologists with experience in inserting indwelling intrathecal catheters. Subjects only required to remain in a horizontal position for the first 24 h after removal of the catheter. CSF and blood samples were collected by interval sampling over a 30-h period. Results   The study was completed by seven of the eight subjects. Six subjects who completed the study reported adverse effects (AEs) which were all mild and from which they recovered during their stay in the clinic. A total of 25 AEs were reported of which 13 were considered to be procedure-related. The procedure was well tolerated by all participating subjects, and the VAS scale scores for headache and back pain were low. CSF samples were analyzed for ACh. All values were above the lowest limit of quantification. On average, the ACh concentration started at a low level but rose between 1 and 2 h after insertion of the catheter and then remained high during the whole sampling period up to 30 h. Conclusion   Serial sampling of CSF in seven healthy volunteers up to 30 h occurred without serious complications and was well tolerated. The CSF collected was of good quality and facilitated the assessment of an Alzheimer’s disease-sensitive biomarker. We conclude that this validation study can form the basis for future patient studies aimed at elucidating disease mechanisms and the pharmacodynamics of drugs in the developmental stage. Content Type Journal Article Category Clinical Trial Pages 1-8 DOI 10.1007/s00228-012-1443-y Authors Izaak den Daas, QPS Netherlands BV, Groningen, The Netherlands Johan Wemer, QPS Netherlands BV, Groningen, The Netherlands Khalid Abou Farha, QPS Netherlands BV, Groningen, The Netherlands Wim Tamminga, QPS Netherlands BV, Groningen, The Netherlands Theo de Boer, QPS Netherlands BV, Groningen, The Netherlands Rob Spanjersberg, Department of Anesthesiology, University Groningen, University Medical Center Groningen, Groningen, The Netherlands Michel M. R. F. Struys, Department of Anesthesiology, University Groningen, University Medical Center Groningen, Groningen, The Netherlands Anthony R. Absalom, Department of Anesthesiology, University Groningen, University Medical Center Groningen, Groningen, The Netherlands Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description:    Mitochondrial fatty acid oxidation (FAO) disorders are caused by defects in one of the FAO enzymes that regulates cellular uptake of fatty acids and free carnitine. An in vitro probe acylcarnitine (IVP) assay using cultured cells and tandem mass spectrometry is a tool to diagnose enzyme defects linked to most FAO disorders. Extracellular acylcarnitine (AC) profiling detects carnitine palmitoyltransferase-2, carnitine acylcarnitine translocase, and other FAO deficiencies. However, the diagnosis of primary carnitine deficiency (PCD) or carnitine palmitoyltransferase-1 (CPT1) deficiency using the conventional IVP assay has been hampered by the presence of a large amount of free carnitine (C0), a key molecule deregulated by these deficiencies. In the present study, we developed a novel IVP assay for the diagnosis of PCD and CPT1 deficiency by analyzing intracellular ACs. When exogenous C0 was reduced, intracellular C0 and total AC in these deficiencies showed specific profiles clearly distinguishable from other FAO disorders and control cells. Also, the ratio of intracellular to extracellular C0 levels showed a significant difference in cells with these deficiencies compared with control. Hence, intracellular AC profiling using the IVP assay under reduced C0 conditions is a useful method for diagnosing PCD or CPT1 deficiency. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s00216-012-6532-3 Authors Jamiyan Purevsuren, Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan Hironori Kobayashi, Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan Yuki Hasegawa, Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan Kenji Yamada, Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan Tomoo Takahashi, Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan Masaki Takayanagi, Division of Metabolism, Chiba Children’s Hospital, Chiba, 266-0007 Japan Toshiyuki Fukao, Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Gifu, 501-1194 Japan Seiji Fukuda, Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan Seiji Yamaguchi, Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya, Izumo, Shimane 693-8501, Japan Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Ionic liquid-salt aqueous two-phase extraction coupled with high-performance liquid chromatography with ultraviolet detection was developed for the determination of sulfonamides in water and food samples. In the procedure, the analytes were extracted from the aqueous samples into the ionic liquid top phase in one step. Three sulfonamides, sulfamerazine, sulfamethoxazole, and sulfamethizole were selected here as model compounds for developing and evaluating the method. The effects of various experimental parameters in extraction step were studied using two optimization methods, one variable at a time and Box–Behnken design. The results showed that the amount of sulfonamides did not have effect on the extraction efficiency. Therefore, a three-level Box–Behnken experimental design with three factors, which combined the response surface modeling, was used to optimize sulfonamides extraction. Under the most favorable extraction parameters, the detection limits ( S / N  = 3) and quantification limits ( S / N  = 10) of the proposed method for the target compounds were achieved within the range of 0.15–0.3 ng/mL and 0.5–1.0 ng/mL from spiked samples, respectively, which are lower than or comparable with other reported approaches applied to the determination of the same compounds. Finally, the proposed method was successfully applied to the determination of sulfonamide compounds in different water and food samples and satisfactory recoveries of spiked target compounds in real samples were obtained. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-6511-8 Authors Juan Han, School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013 China Yun Wang, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China Yan Liu, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China Yanfang Li, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China Yang Lu, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China Yongsheng Yan, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China Liang Ni, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A new simple and reliable method combining an acetonitrile partitioning extractive procedure followed by dispersive solid-phase cleanup (QuEChERS) with dispersive liquid–liquid microextraction (DLLME) and further gas chromatography mass spectrometry analysis was developed for the simultaneous determination of bisphenol A (BPA) and bisphenol B (BPB) in canned seafood samples. Besides the great enrichment factor provided, the final DLLME extractive step was designed in order to allow the simultaneous acetylation of the compounds required for their gas chromatographic analysis. Tetrachloroethylene was used as extractive solvent, while the acetonitrile extract obtained from QuEChERS was used as dispersive solvent, and anhydride acetic as derivatizing reagent. The main factors influencing QuEChERS and DLLME efficiency including nature of QuEChERS dispersive-SPE sorbents, amount of DLLME extractive and dispersive solvents and nature and amount of derivatizing reagent were evaluated. DLLME procedure provides an effective enrichment of the extract, allowing the required sensitivity even using a single quadropole MS as detector. The optimized method showed to be accurate (〉68 % recovery), reproducible (〈21 % relative standard deviation) and sensitive for the target analytes (method detection limits of 0.2 μg/kg for BPA and 0.4 μg/kg for BPB). The screening of several canned seafood samples commercialized in Portugal (total = 47) revealed the presence of BPA in more than 83 % of the samples with levels ranging from 1.0 to 99.9 μg/kg, while BPB was found in only one sample at a level of 21.8 μg/kg. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-6389-5 Authors S. C. Cunha, REQUIMTE, Laboratory of Bromatology and Hydrology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal C. Cunha, REQUIMTE, Laboratory of Bromatology and Hydrology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal A. R. Ferreira, REQUIMTE, Laboratory of Bromatology and Hydrology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal J. O. Fernandes, REQUIMTE, Laboratory of Bromatology and Hydrology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A polydimethylsiloxane microfluidic chip has been developed for the estimation of toxic heavy metals based on measurement of mobility of marine microalgae. The chip is mainly composed of an upstream concentration gradient generator and a downstream perfusion-based chemotatic module. The processes of toxic liquid dilution and diffusion, microalgal culturing, cell stimulation, and online screening can be integrated in this chip, which makes it an attractive approach to simplify toxicity testing procedures. The microalgal motility was adopted as a microfluidic bioassay signal and was evaluated as the percentage of motile cells, curvilinear velocity, average path velocity, and straight line velocity. Two mobile marine microalgae, Platymonas subcordiformis and Platymonas helgolandica var. tsingtaoensis , were confined in the chemotatic module and stimulated by the eight concentration gradients of Cu and Cd generated by the concentration gradient generator. In all cases, a toxic response was detected (i.e., a dose-related inhibition of motility was observed). Only 1.5 h was needed to predict EC 50 values. Thus, the microfluidic chip developed was proved to be useful as a simple and rapid approach in heavy metal detection and might be expanded as a conventional test method in environmental toxicity assessment. Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-6408-6 Authors Guoxia Zheng, Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116622, China Yunhua Wang, Dalian University, Dalian, Liaoning 116622, China Jianhua Qin, Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116622, China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Owing to their favorable porous structure with pore size distribution shifted towards large flow-through pores, organic polymer monoliths have been mainly employed for the separation of macromolecules in gradient elution liquid chromatography. The absence of significant amounts of small pores with a stagnant mobile phase and the resulting low surface area were considered as the main reason for their poor behavior in the isocratic separation of small molecules. Several recent efforts have improved the separation power of organic polymer monoliths for small molecules offering column efficiency up to tens of thousands of plates per meter. These attempts include optimization of the composition of polymerization mixture, including the variation of functional monomer, the cross-linking monomer, and the porogen solvents mixture, adjustment of polymerization temperature, and time. Additionally, post-polymerization modifications including hypercross-linking and the use of carbon nanostructures showed significant improvement in the column properties. This review describes recent developments in the preparation of organic polymer monoliths suitable for the separation of small molecules in the isocratic mode as well as the main factors affecting the column efficiency. Content Type Journal Article Category Review Pages 1-9 DOI 10.1007/s00216-012-6392-x Authors Jiri Urban, Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic Pavel Jandera, Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Purpose   To analyse, in older community-dwelling people living in Italy’s Lombardy region, 8-year trends in new users of spironolactone co-prescribed with angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs); blood test monitoring; and independent predictors of appropriate blood test monitoring. Methods   The region’s administrative health database from 2001 to 2008 was used to retrieve yearly frequencies of subjects aged 65+ who started this co-prescription. Multivariate analyses were adjusted for age, sex, local health unit, treatment with beta-blockers, drugs for diabetes, and polypharmacy (i.e., exposure to five or more different drugs). Results   Only new users of spironolactone co-prescribed with ARBs increased from 2001 to 2008 ( P  〈 0.001). In the 6 months before starting the co-prescriptions 96 to 100% of patients measured serum creatinine (mean 99.3%), sodium (97.3%) and potassium (98.6%). Within 3 months of starting the co-prescriptions 96 to 99% of patients measured serum sodium (mean 97.3%) and potassium (98.6%), but on average only 48% of them (range 43 to 53%) measured serum creatinine, with an increase over time (odds ratio [change in regression per year] = 1.03, 95% CI 1.02–1.05, P  〈 0.001). At multivariate analysis polypharmacy was found to be the only independent predictor of such creatinine monitoring ( P  〈 0.001). Conclusions   Our results support the need for greater awareness within the medical community of the potential renal toxicity of the association of spironolactone with ACE-Is and/or ARBs. Adequate short-term monitoring of serum creatinine in all older community-dwelling people who receive such co-prescription is necessary in order to ensure safe usage of these medications. Content Type Journal Article Category Pharmacoepidemiology and Prescription Pages 1-9 DOI 10.1007/s00228-012-1401-8 Authors Claudio Bilotta, Geriatric Medicine Outpatient Service, Department of Urban Outpatient Services, Istituti Clinici di Perfezionamento Hospital, viale Doria 52, 20124 Milan, Italy Carlotta Franchi, Laboratory for Quality Assessment of Geriatric Therapies and Services, Mario Negri Institute for Pharmacological Research, via La Masa 19, 20156 Milan, Italy Alessandro Nobili, Laboratory for Quality Assessment of Geriatric Therapies and Services, Mario Negri Institute for Pharmacological Research, via La Masa 19, 20156 Milan, Italy Paola Nicolini, Thoraco-Pulmonary and Cardiocirculatory Department, University of Milan, via F. Sforza 35, 20122 Milan, Italy Codjo Djignefa Djade, Laboratory for Quality Assessment of Geriatric Therapies and Services, Mario Negri Institute for Pharmacological Research, via La Masa 19, 20156 Milan, Italy Mauro Tettamanti, Laboratory for Quality Assessment of Geriatric Therapies and Services, Mario Negri Institute for Pharmacological Research, via La Masa 19, 20156 Milan, Italy Ida Fortino, Regional Health Ministry Lombardy Region, Piazza Città di Lombardia 1, 20124 Milan, Italy Angela Bortolotti, Regional Health Ministry Lombardy Region, Piazza Città di Lombardia 1, 20124 Milan, Italy Luca Merlino, Regional Health Ministry Lombardy Region, Piazza Città di Lombardia 1, 20124 Milan, Italy Carlo Vergani, Department of Medical Sciences, Geriatric Medicine, University of Milan, via Pace 9, 20122 Milan, Italy Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description: Purpose   Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely used in clinical practice. Recent data have indicated that high therapeutic citalopram doses may cause electrocardiographic abnormalities, and the regulatory authorities have amended its licenced dosage. The present manuscript reviews the available data concerning citalopram and cardiac toxicity. Methods   Published data concerning the cardiac effects of citalopram were ascertained, and clinical data were considered separately between adverse effects arising from therapeutic use versus toxicity in the setting of intentional overdose. Results   The occurrence of electrocardiographic abnormalities has long been recognised as a complication of acute citalopram overdose; a dose-effect relationship for QT prolongation has been described in a number of large case series, including several cases of torsades de pointes. In contrast, few data indicate the occurrence of QT prolongation and arrhythmia after therapeutic doses, and a dose-effect relationship within the therapeutic range has only recently been established. Citalopram is more likely to cause QT prolongation in patients with metabolic disturbance or pre-existing cardiac disease. Conclusions   A dose-effect relationship for QT prolongation exists across a broad range of citalopram doses, such that caution must be exercised when prescribing high doses or if there are co-existent risk factors for QT effects. The available data illustrate how clinical toxicity data may offer an earlier signal of cardiac effects than ascertained from conventional pharmacovigilance methods. Content Type Journal Article Category Review Article Pages 1-6 DOI 10.1007/s00228-012-1408-1 Authors M. J. Cooke, Pharmacy Department, York Teaching Hospital NHS Foundation Trust, Wigginton Road, York, YO31 8HE UK W. S. Waring, Acute Medical Unit, York Teaching Hospital NHS Foundation Trust, Wigginton Road, York, YO31 8HE UK Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description: Objective   Our aim was to characterize Adverse Drug Reactions (ADRs) related to drug–drug interactions (DDIs) related to involvement of cytochrome P450 (CYP450) isoenzymes in a pharmacovigilance database. Methods   ADRs recorded by Midi-Pyrénées PharmacoVigilance center (France) between 1 January and 31 August 2008 were extracted from the French PharmacoVigilance Database (FPVD). Results   Among the 1,205 reported ADRs, 16 (1.3 %), can be explained by involvement of CYP450 isoenzymes (including 4 “serious”). All interactions involved CYP inhibitors, mainly for CYP3A4/5. Conclusion   The percentage of ADRs reported in the pharmacovigilance database and related to CYP450-induced DDIs appears to be relatively low (~ 1–2 %). Content Type Journal Article Category Pharmacoepidemiology and Prescription Pages 1-4 DOI 10.1007/s00228-012-1394-3 Authors Anne Charlotte Danton, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France François Montastruc, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France Agnès Sommet, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France Geneviève Durrieu, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France Haleh Bagheri, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France Emmanuelle Bondon-Guitton, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France Maryse Lapeyre-Mestre, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France Jean-Louis Montastruc, Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description: Purpose   We previously reported that chronic heart failure (CHF) treatments reduce the duration of hospitalisation, even in elderly patients. The present study aimed to determine whether CHF treatment also provides long-term benefits in terms of reduced mortality at 8 years. Methods   A cohort of 281 patients who were admitted to a French teaching hospital with a main diagnosis of CHF were followed through the health insurance databases for 1 year and through the national mortality database for 8 years. Results   Diuretics (236 patients, 84 %) and angiotensin-converting enzyme (ACE) inhibitors (193 patients, 69 %) were the most-frequently prescribed medications. The median duration of survival was 46 months. Mortality rates were significantly lower for patients administered beta-blockers (59 %) and statins (56 %) than for patients not exposed to these drugs (82 %, p  〈 0.001 and 78 %, p  = 0.001 respectively). No significant differences in mortality were observed for spironolactone, diuretics or ACE inhibitors. After adjustment, beta-blocker treatment remained associated with a significantly lower risk of mortality (hazard ratio, HR = 0.54 [0.34–0.84]). After adjustment, the use of two or three CHF drugs was associated with longer survival (HR = 0.53 [0.36–0.77]) than the use of zero or one CHF drug. Statins were also associated with longer survival after adjustment (HR = 0.53 [0.31–0.89]). In patients 75 years of age or older ( n  = 73), only beta-blocker treatment was associated with a significantly lower risk of mortality (HR = 0.31 [0.16–0.63]) in multivariate analysis. Conclusions   The use of beta-blockers was associated with better survival rates. The use of statins was also associated with better survival at 8 years. Randomised controlled trials are required to confirm these observations. Content Type Journal Article Category Pharmacoepidemiology and Prescription Pages 1-8 DOI 10.1007/s00228-012-1400-9 Authors Patrick Maison, Service de Pharmacologie Clinique, AP-HP, Hôpital H. Mondor—A. Chenevier, Créteil, 94000 France Gaelle Desamericq, Service de Pharmacologie Clinique, AP-HP, Hôpital H. Mondor—A. Chenevier, Créteil, 94000 France François Hemery, Département d’information médicale, AP-HP, Hôpital H. Mondor—A. Chenevier, Créteil, 94000 France Nicole Elie, National Health Insurance Fund, Créteil, France Aldo Del’Volgo, National Health Insurance Fund, Créteil, France Jean Luc Dubois-Randé, Fédération de Cardiologie, AP-HP, Hôpital H. Mondor—A. Chenevier, Créteil, 94000 France Luc Hittinger, Fédération de Cardiologie, AP-HP, Hôpital H. Mondor—A. Chenevier, Créteil, 94000 France Isabelle Macquin-Mavier, Service de Pharmacologie Clinique, AP-HP, Hôpital H. Mondor—A. Chenevier, Créteil, 94000 France Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description:    The National Institute of Standards and Technology (NIST) has been certifying lots, or series, of Standard Reference Materials (SRMs) containing ambient level methane in air for over 40 years. The historical record contains six traditional series of SRM 1658 (1 μmol mol −1 ), five of SRM 1660 (4 μmol mol −1 ), and seven of SRM 1659 (10 μmol mol −1 ) methane in air. All series of any one particular SRM can be linked to each other through the historical suites of gravimetric primary standard mixtures (PSMs) developed at NIST. One gas mixture cylinder from a series is chosen as the lot standard (LS), retained and held at NIST, and periodically compared to the PSMs to assure its stability. Recently, 6 of the original 18 LS still in service in the Gas Metrology Group inventory, and cylinder samples held at NIST from 6 other SRM lots, were analyzed against a newly prepared suite of PSMs using cavity ring-down spectroscopy. Data were analyzed using a generalized least squares linear regression. The results indicate that, within the original 95 % confidence intervals, the methane concentration has remained the same for all the SRM LS and lot samples. The current predicted concentrations of the LS and samples for SRMs 1659 and 1660 are within 0.002 to 0.051 μmol mol −1 , or ≤0.5 %, relative of the original certificate value. SRM 1658 LS and samples are within 0.0001 to 0.0023 μmol mol −1 , or ≤0.2 % relative. These results illustrate the consistency, repeatability, and stability of these methane in air SRMs over the historical 35+-year record. It also demonstrates that the historical gravimetric primary methane in air suites have remained accurate and consistent over time. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s00216-012-6397-5 Authors George C. Rhoderick, Analytical Chemistry Division, Materials and Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20899-8393, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A fast reversed-phase liquid chromatography-electrospray ionization triple quadrupole mass spectrometry method was developed for the molecular species profiling of glycerophosphocholine (GPC) and sphingomyelin (SM) in total lipid extracts. A two-stage mass spectrometry strategy was adopted to analyze in detail the composition of lipid molecular species. Precursor ion analysis was first conducted to obtain the preliminary composition profile of the phosphorylcholine-containing lipid. The product ion spectra were sequentially acquired for each recorded signal to determine the molecular structure of the lipid. A total of 150 GPCs and 12 SMs were identified in the fetal mouse lung with relative amounts ranging from 13.7 % to less than 0.002 % (normalizing by the total signal response). A column packed with core–shell particles was used to obtain excellent chromatographic separation with a shorter time demand in a conventional high-performance liquid chromatography system. Considering the compromise between the chromatographic efficiency and the electrospray signal response, the optimization of the mobile phase improves the chromatographic plate number to approximately 40,000 and the detection limits to less than 0.001 mg/L. The applicability of the method was validated through a study of chemically induced early lung maturation. The metabolic alteration in the fetal mouse lung was clearly reflected in the GPC and SM composition with several characteristics of the molecular structure that related to the character of the phospholipid layer upon the epithelial lining of alveoli and the relevant cell function. The results indicated that this analytical strategy is reliable for comprehensive molecular species profiling of GPC and SM and might be extended to the analysis of other phospholipids. Figure  Glycerophosphocholine and sphingomyelin molecular species profiling using a fast HPLC/QqQ-MS method adopting a two-stage mass spectrometry strategy composed of preliminary phosphorylcholine-containing lipid profiling and sequential lipid molecular structure determination Content Type Journal Article Category Original Paper Pages 1-13 DOI 10.1007/s00216-012-6414-8 Authors Chuan-Ho Tang, National Museum of Marine Biology and Aquarium, 2 Houwan Rd., Checheng, Pingtung 944, Taiwan Po-Nien Tsao, Department of Pediatrics, National Taiwan University Hospital, Taipei, 100 Taiwan Ching-Yu Lin, Institute of Environmental Health, National Taiwan University, Taipei, 100 Taiwan Lee-Shing Fang, Department of Sport, Health, and Leisure, Cheng Shiu University, Kaohsiung, 833 Taiwan Shu-Hui Lee, Central of General Education, National Kaohsiung Marine University, Kaohsiung, 811 Taiwan Wei-Hsien Wang, National Museum of Marine Biology and Aquarium, 2 Houwan Rd., Checheng, Pingtung 944, Taiwan Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Monitoring single molecules in living cells is becoming a powerful tool for study of the location, dynamics, and kinetics of individual biomolecules in real time. In recent decades, several optical imaging techniques, for example epi-fluorescence microscopy, total internal reflection fluorescence microscopy (TIRFM), confocal microscopy, quasi-TIRFM, and single-point edge excitation subdiffraction microscopy (SPEED), have been developed, and their capability of capturing single-molecule dynamics in living cells has been demonstrated. In this review, we briefly summarize recent advances in the use of these imaging techniques for monitoring single-molecules in living cells for a better understanding of important biological processes, and discuss future developments. Content Type Journal Article Category Trends Pages 1-7 DOI 10.1007/s00216-012-6373-0 Authors Wangxi Luo, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructures and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, 2 Zhongguancun North First Street, 100190 Beijing, China Kangmin He, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructures and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, 2 Zhongguancun North First Street, 100190 Beijing, China Tie Xia, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructures and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, 2 Zhongguancun North First Street, 100190 Beijing, China Xiaohong Fang, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructures and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, 2 Zhongguancun North First Street, 100190 Beijing, China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Dynorphin A 1–17 (DYN A) is an endogenous neuropeptide that is of interest due to its diverse roles in analgesia, inflammation and addiction. Upon release, DYN A is subject to metabolism by a range of enzymes and its biotransformation is dependent on the site and environment into which it is released. In this study, we investigated the biotransformation of DYN A in rat inflamed tissue at pH 7.4 and 5.5, in rat serum and in trypsin solution. DYN A-porcine was incubated at 37 °C in each matrix over a range of incubation periods. The resultant fragments were separated using a C4 column and detected by mass spectrometry using total ion current mode. Incubation of DYN A in trypsin solution and in rat serum resulted in 6 and 14 fragments, respectively. Incubation in inflamed rat paw tissue occasioned 21 fragments at pH 7.4 and 31 fragments at pH 5.5. Secondary breakdown of some larger primary fragments was also observed in this study. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-6406-8 Authors M. Morgan, School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia H. M. D. R. Herath, School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia P. J. Cabot, School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia P. N. Shaw, School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia A. K. Hewavitharana, School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The occurrence of microorganisms in water due to contamination is a health risk and control thereof is a necessity. Conventional detection methods may be misleading and do not provide rapid results allowing for immediate action. The quantitative polymerase chain reaction (qPCR) method has proven to be an effective tool to detect and quantify microorganisms in water within a few hours. Quantitative PCR assays have recently been developed for the detection of specific adeno- and polyomaviruses, bacteria and protozoa in different water sources. The technique is highly sensitive and able to detect low numbers of microorganisms. Quantitative PCR can be applied for microbial source tracking in water sources, to determine the efficiency of water and wastewater treatment plants and act as a tool for risk assessment. Different qPCR assays exist depending on whether an internal control is used or whether measurements are taken at the end of the PCR reaction (end-point qPCR) or in the exponential phase (real-time qPCR). Fluorescent probes are used in the PCR reaction to hybridise within the target sequence to generate a signal and, together with specialised systems, quantify the amount of PCR product. Quantitative reverse transcription polymerase chain reaction (q-RT-PCR) is a more sensitive technique that detects low copy number RNA and can be applied to detect, e.g. enteric viruses and viable microorganisms in water, and measure specific gene expression. There is, however, a need to standardise qPCR protocols if this technique is to be used as an analytical diagnostic tool for routine monitoring. This review focuses on the application of qPCR in the detection of microorganisms in water. Content Type Journal Article Category Review Pages 1-18 DOI 10.1007/s00216-012-6399-3 Authors Marelize Botes, Department of Microbiology, University of Stellenbosch, Private Bag XI, Matieland 7602, Stellenbosch, Western Cape 7602, South Africa Michéle de Kwaadsteniet, Department of Microbiology, University of Stellenbosch, Private Bag XI, Matieland 7602, Stellenbosch, Western Cape 7602, South Africa Thomas Eugene Cloete, Department of Microbiology, University of Stellenbosch, Private Bag XI, Matieland 7602, Stellenbosch, Western Cape 7602, South Africa Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Two approaches are proposed to measure the effect of different experimental factors (such as the modifier concentration and temperature) on the elution strength and peak shape in reversed-phase liquid chromatography, which quantify the percentage change in the retention factor and peak width (referred to the weakest conditions) per unit change in the experimental factor. The approaches were applied to the separation of a set of flavonoids with aqueous micellar mobile phases of the surfactant Brij-35 (polyoxyethylene(23)dodecanol), in comparison with acetonitrile–water mixtures, using an Eclipse XDB-C18 column. The particular interaction of each flavonoid with the oxyethylene chains of Brij-35 molecules (adsorbed on the stationary phase or forming micelles) changed the elution window, distribution of chromatographic peaks and partitioning kinetics, depending on the hydroxyl substitution in the aromatic rings of flavonoids. At 25 °C, peak shape with Brij-35 mobile phases was significantly poorer with regard to acetonitrile–water mixtures. At increasing temperature, the efficiency of Brij-35 increased, approaching at 80 °C the values obtained at equilibrium conditions, already reached with acetonitrile at 25 °C. Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s00216-012-6387-7 Authors J. J. Baeza-Baeza, Departamento de Química Analítica, Universidad de Valencia, c/Dr. Moliner 50, 46100 Burjassot, Spain Y. Dávila, Departamento de Química Física, Universidad Nacional de San Luis, D5700HHW San Luis, Argentina J. J. Fernández-Navarro, Departamento de Química Analítica, Universidad de Valencia, c/Dr. Moliner 50, 46100 Burjassot, Spain M. C. García-Álvarez-Coque, Departamento de Química Analítica, Universidad de Valencia, c/Dr. Moliner 50, 46100 Burjassot, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Purpose   The objective of this study was to compare different methods of adjusted indirect comparisons that can be used to investigate the relative bioavailability of different generic products. To achieve this goal, generic artemether/lumefantrine 20/120 mg tablets that have been prequalified by the World Health Organization (WHO) were selected as model products for study. Methods   Data from three bioequivalence studies conducted independently that compared three generics with the same reference product were used to indirectly determine the relative bioavailability between the generics themselves. Results   The different methods of indirect comparison examined in this study provide consistent results. Methods based on the assumption of a large sample size give slightly narrower 90 % confidence intervals. Therefore, the use of methods based on the t test is recommended. Given the precision of the area under the time–concentration curve (AUC) data, it is possible to conclude that the extent of exposure of artemether and lumefantrine is bioequivalent between the different generics studied. However, given the precision of the drug peak concentration (C max ) data, it is not possible to demonstrate equivalence within the conventional acceptance range for all comparisons; it is possible to conclude bioequivalence within the widened acceptance range 75–133 %. Conclusions   From a clinical viewpoint, not only are these prequalified generics bioequivalent and interchangeable with the reference product (Coartem, Novartis), but also the existing indirect evidence makes it possible to conclude that these WHO prequalified products are bioequivalent between themselves with respect to the AUC. The lack of the necessary precision to demonstrate bioequivalence between generics with respect to the C max within the conventional acceptance range does not preclude considering them as interchangeable, if necessary, since C max is considered to be of less clinical relevance for the relevant therapy. Content Type Journal Article Category Pharmacokinetics and Disposition Pages 1-8 DOI 10.1007/s00228-012-1396-1 Authors Luther Gwaza, Evaluation and Registration Unit, Medicines Control Authority of Zimbabwe, Harare, Zimbabwe John Gordon, Division of Biopharmaceutics Evaluation, Bureau of Pharmaceutical Sciences, Therapeutic Products Directorate, Health Canada, Ottawa, Canada Jan Welink, Medicines Evaluation Board, Utrecht, The Netherlands Henrike Potthast, Subdepartment of Biostatistics and Pharmacokinetics, Federal Insitute for Drugs and Medical Devices, Bonn, Germany Henrik Hansson, Efficacy and Safety Department 1, Medical Products Agency, Uppsala, Sweden Matthias Stahl, The Prequalification of Medicines Programme Quality Assurance & Safety: Medicines Essential Medicines and Health Products, World Health Organization, Geneva, Switzerland Alfredo García-Arieta, División de Farmacología y Evaluación Clínica, Subdirección de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios, C/ Campezo 1. Edificio 8, Planta 2 Oeste, 28022 Madrid, Spain Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description: Purpose   To present concept, methods and use of a knowledge database providing assessments of potential fetal risks for all drugs on the Swedish market. Methods   Assessments of fetal risks are made primarily by analyzing prospective epidemiological data from the Swedish Medical Birth Register on drug intake in relation to birth outcome. This is complemented by evaluation of the scientific literature. Following standardized working procedures, a statement is compiled for each substance, which is also classified into one of three categories depending on the estimated risk level. The final documents include drug product names on the market, via linkage to a medicinal products register. The information is free and published on the website www.janusinfo.se . It can also be used as an integrated part of electronic health records. Results   The database covers assessments of fetal risks for close to 1,250 medicinal drug substances on the Swedish market. Each year, 96,000 searches are made, which might be compared to the around 100,000 children born in Sweden yearly. Apart from the Swedish Physicians’ Desk Reference (Fass), the database is the most commonly used resource among specialists within gynaecology and perinatal medicine for information on drugs during pregnancy. Conclusions   A non-commercial knowledge base with assessments of fetal risk of different drugs is valued by health care professionals and is used extensively in Sweden. Based on analyses of national health registers, the database provides unique information on teratogenic drug risks. Content Type Journal Article Category Pharmacoepidemiology and Prescription Pages 1-11 DOI 10.1007/s00228-012-1399-y Authors Ulrika Nörby, E-health and Strategic IT, Public Healthcare Administration, Stockholm County Council, P.O. Box 17533, SE-118 91 Stockholm, Sweden Karin Källén, Tornblad Institute, University of Lund, Lund, Sweden Birgit Eiermann, Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden Seher Korkmaz, E-health and Strategic IT, Public Healthcare Administration, Stockholm County Council, P.O. Box 17533, SE-118 91 Stockholm, Sweden Birger Winbladh, Department of Clinical Sciences and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden Lars L. Gustafsson, Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description:    The study of metal–protein interactions is an expanding field of research investigated by bioinorganic chemists as it has wide applications in biological systems. Very recently, it has been reported that it is possible to study metal–protein interactions by immobilizing biomolecules on metal surfaces and applying experimental approaches based on plasmonics which have usually been used to investigate protein–protein interactions. This is possible because the electronic structure of metals generates plasmons whose properties can be exploited to obtain information from biomolecules that interact not only with other molecules but also with ions in solution. One major challenge of such approaches is to immobilize the protein to be studied on a metal surface with preserved native structure. This review reports and discusses all the works that deal with such an expanding new field of application of plasmonics with specific attention to surface plasmon resonance, highlighting the advantages and drawbacks of such approaches in comparison with other experimental techniques traditionally used to study metal–protein interactions. Figure  Plasmonics is a powerful tool for the study of metal ion-protein interactions Content Type Journal Article Category Review Pages 1-11 DOI 10.1007/s00216-012-6421-9 Authors Giuseppe Grasso, Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy Giuseppe Spoto, Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: ProSafeBeef and anthelmintic drug residues—a case study in collaborative application of multi-analyte mass spectrometry to enhance consumer safety Content Type Journal Article Category Feature Article Pages 1623-1630 DOI 10.1007/s00216-012-6310-2 Authors Kevin M. Cooper, Institute of Agri-Food and Land Use, Queen’s University Belfast, David Keir Building, 18-30 Malone Road, Belfast, BT9 5BN UK D. Glenn Kennedy, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stoney Road, Stormont, Belfast, BT4 3SD UK Martin Danaher, Food Safety Department, Teagasc Food Research Centre, Ashtown, Dublin 15, Ireland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642 Journal Volume Volume 404 Journal Issue Volume 404, Numbers 6-7

Description:    In the present study, Fourier transform infrared (FTIR) imaging and data analysis methods were combined to study morphological and molecular patterns of St. John's wort ( Hypericum perforatum ) in detail. For interpretation, FTIR imaging results were correlated with histological information gained from light microscopy (LM). Additionally, we tested several evaluation processes and optimized the methodology for use of complex FTIR microscopic images to monitor molecular patterns. It is demonstrated that the combination of the used spectroscopic method with LM enables a more distinct picture, concerning morphology and distribution of active ingredients, to be gained. We were able to obtain high-quality FTIR microscopic imaging results and to distinguish different tissue types with their chemical ingredients. Content Type Journal Article Category Original Paper Pages 1771-1778 DOI 10.1007/s00216-012-6296-9 Authors V. A. Huck-Pezzei, Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria J. D. Pallua, Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria C. Pezzei, Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria L. K. Bittner, Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria S. A. Schönbichler, Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria G. Abel, Bionorica SE, Kerschensteinerstrasse 11-18, 92318 Neumarkt, Germany M. Popp, Bionorica SE, Kerschensteinerstrasse 11-18, 92318 Neumarkt, Germany G. K. Bonn, Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria C. W. Huck, Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80/82, 6020 Innsbruck, Austria Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642 Journal Volume Volume 404 Journal Issue Volume 404, Numbers 6-7

Description:    While conjugated polymer nanoparticles (CPNs) have been widely touted as ultra-bright labels for biological imaging, no direct comparative measurements of their intracellular brightness have been reported. Simple in vitro comparisons are not definitive since fluorophore brightness in vitro may not correspond with intracellular brightness. We have compared the fluorescence brightness of J774A.1 cells loaded with 24 nm methoxy-capped 2,000  M r polyethylene glycol lipid PFBT nanoparticles (PEG lipid-PFBT CPNs) to cells loaded with carboxy-functionalized quantum dots (Qdots) or a dextran-linked small molecule organic dye, Alexa Fluor 488 dextran (AF488-dex). Under conditions likely to be used for biological imaging or flow cytometry, these CPNs are 175× brighter than Qdots and 1,400× brighter than AF488-dex in cells. Evaluation of the minimum incubation concentration required for detection of nanoparticle fluorescence with a commercial flow cytometer indicated that the limit of detection for PEG lipid-PFBT CPNs was 19 pM (86 ppb), substantially lower than values obtained for Qdots (980 pM) or AF488-dex (11.2 nM). Investigation of the mechanism of cellular uptake of the three fluid-phase labels indicates that these particles are passively taken into macrophage cells via macropinocytosis without interaction with cell surface receptors, and ultimately localize in lysosomes. In addition, no cytotoxicity could be observed at any of the CPN concentrations tested. Together, these data suggest that these CPNs are appropriate and attractive candidates as fluid-phase markers with significantly greater fluorescence brightness than existing dyes or nanoparticles. We expect that these CPNs will find application in both imaging and flow cytometry. Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s00216-012-6441-5 Authors Lawrence P. Fernando, Department of Chemistry, Clemson University, Clemson, SC 29634, USA Prakash K. Kandel, Department of Chemistry, Clemson University, Clemson, SC 29634, USA P. Christine Ackroyd, Department of Chemistry, Clemson University, Clemson, SC 29634, USA Kenneth A. Christensen, Department of Chemistry, Clemson University, Clemson, SC 29634, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Several problems for the direct electrochemical oxidation of reduced glutathione (GSH) challenge the usage of electroanalytical techniques for its determination. In this work, the electrochemical oxidation of GSH catalyzed by gold nanoparticles electrodeposited on Nafion modified carbon paste electrode in 0.04 mol L −1 universal buffer solution (pH 7.4) is proved successful. The effect of various experimental parameters including pH, scan rate and stability on the voltammetric response of GSH was investigated. At the optimum conditions, the concentration of GSH was determined using differential pulse voltammetry (DPV) in two concentration ranges: 0.1 × 10 −7 to 1.6 × 10 −5  mol L −1 and 2.0 × 10 −5 to 2.0 × 10 −4  mol L −1 with correlation coefficients 0.9988, 0.9949 and the limit of detections (LOD) are 3.9 × 10 −9  mol L −1 and 8.2 × 10 −8  mol L −1 , respectively, which confirmed the sensitivity of the electrode. The high sensitivity, wide linear range, good stability and reproducibility, and the minimal surface fouling make this modified electrode useful for the determination of spiked GSH in urine samples and in tablet with excellent recovery results obtained. Content Type Journal Article Category Original Paper Pages 1661-1672 DOI 10.1007/s00216-012-6276-0 Authors Nada F. Atta, Department of Chemistry, Faculty of Science, University of Cairo, Giza, 12613 Egypt Ahmed Galal, Department of Chemistry, Faculty of Science, University of Cairo, Giza, 12613 Egypt Shereen M. Azab, National Organization for Drug Control and Research, Giza, Egypt Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642 Journal Volume Volume 404 Journal Issue Volume 404, Numbers 6-7

Description:    This work describes the development, optimization, and validation of a new method for the simultaneous determination of a wide range of pharmaceuticals (beta-blockers, lipid regulators…) and personal care products (fragrances, UV filters, phthalates…) in both aqueous and solid environmental matrices. Target compounds were extracted from sediments using pressurized hot water extraction followed by stir bar sorptive extraction. The first stage was performed at 1,500 psi during three static extraction cycles of 5 min each after optimizing the extraction temperature (50–150 °C) and addition of organic modifiers (% methanol) to water, the extraction solvent. Next, aqueous extracts and water samples were processed using polydimethylsiloxane bars. Several parameters were optimized for this technique, including extraction and desorption time, ionic strength, presence of organic modifiers, and pH. Finally, analytes were extracted from the bars by ultrasonic irradiation using a reduced amount of solvent (0.2 mL) prior to derivatization and gas chromatography–mass spectrometry analysis. The optimized protocol uses minimal amounts of organic solvents (〈10 mL/sample) and time (≈8 h/sample) compared to previous existing methodologies. Low standard deviation (usually below 10 %) and limits of detection (sub-ppb) vouch for the applicability of the methodology for the analysis of target compounds at trace levels. Once developed, the method was applied to determine concentrations of these compounds in several types of sample (wastewater, seawater, pore water, and sediment) from Cadiz Bay (SW Spain). To our knowledge, these findings represent the first information available on the presence of some of the target compounds in the marine environment. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-6453-1 Authors Marina G. Pintado-Herrera, Departamento de Química Física, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz - Campus de Excelencia Internacional del Mar (CEI·MAR), Campus Río San Pedro s/n, 11510 Puerto Real, Cádiz, Spain Eduardo González-Mazo, Departamento de Química Física, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz - Campus de Excelencia Internacional del Mar (CEI·MAR), Campus Río San Pedro s/n, 11510 Puerto Real, Cádiz, Spain Pablo A. Lara-Martín, Departamento de Química Física, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz - Campus de Excelencia Internacional del Mar (CEI·MAR), Campus Río San Pedro s/n, 11510 Puerto Real, Cádiz, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    In the age of the Internet, the variety of drugs offered online is constantly increasing, and new drugs emerge every month. One group of drugs showing such an enormous increase is that of synthetic cannabinoids. Since their first identification in ‘herbal mixtures’, new structural modifications continue to appear on the market. In order to keep up with this process, toxicological screening methods need to be up to date. This can become extremely difficult if no reference material is available. In this article, a fast and effective way to extract and purify synthetic cannabinoids from ‘herbal mixtures’ is presented. This method opens a new opportunity for a timely reaction by obtaining reference material straight out of the ‘herbal mixtures’ ordered via the Internet. Isolation was carried out on a flash chromatography system with gradient elution on a C18 column using methanol and 0.55 % formic acid as mobile phases. The obtained purity of all compounds exceeded 99 %. In addition to the isolation of single compounds, the method proved to be suitable for the separation of various synthetic cannabinoids in one mixture, including the diastereomers cis - and trans -CP-47,497-C8. This approach for obtaining pure standards of new drugs proved to be effective, inexpensive and much quicker than waiting for the substances to be commercially available as reference material. Figure  Flash chromatography method for the isolation of synthetic cannabinoids from ‘herbal mixtures’ to obtain pure reference standards. Content Type Journal Article Category Original Paper Pages 1-7 DOI 10.1007/s00216-012-6462-0 Authors Bjoern Moosmann, Institute of Forensic Medicine, Department of Forensic Toxicology, University Medical Center Freiburg, Albertstr. 9, 79104 Freiburg, Germany Stefan Kneisel, Institute of Forensic Medicine, Department of Forensic Toxicology, University Medical Center Freiburg, Albertstr. 9, 79104 Freiburg, Germany Ariane Wohlfarth, Institute of Forensic Medicine, Department of Forensic Toxicology, University Medical Center Freiburg, Albertstr. 9, 79104 Freiburg, Germany Volker Brecht, Institute of Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany Volker Auwärter, Institute of Forensic Medicine, Department of Forensic Toxicology, University Medical Center Freiburg, Albertstr. 9, 79104 Freiburg, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Liquid chromatography coupled to tandem mass spectrometry has been compared to shotgun analysis with the objective of finding the best compromise for a single run analysis of whole cell phospholipids. Hydrophilic interaction liquid chromatography (HILIC), normal phase (NP), and reversed phase (RP) liquid chromatography were evaluated with reference phospholipids belonging to phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylserine (PS) classes. NP-HPLC- and RP-HPLC-ESI-MS/MS were applied to yeast phospholipidome analysis, using a wild-type strain and two strains defective for acyltransferases that are known to be involved in de novo phospholipid synthesis or phospholipid remodeling. The MRM mode was used for relative quantitation of individual compounds based on reference phospholipids bearing fatty acid chains with an odd number of carbon atoms. Combined LC-MS/MS was found superior to shotgun analysis, leading to a larger number of quantified species than shotgun analysis. Finally, RP-HPLC-MS/MS was the preferred method for its higher selectivity, robustness, and better repeatability. Content Type Journal Article Category Original Paper Pages 1-11 DOI 10.1007/s00216-012-6466-9 Authors Corinne Buré, Chimie Biologie des Membranes et Nanoobjets CBMN—UMR 5248 Centre de Génomique Fonctionnelle Université Bordeaux 2, Université de Bordeaux, 146, rue Léo Saignat, 33076 Bordeaux cedex, France Sophie Ayciriex, Laboratoire de Biogenèse Membranaire, UMR 5200 CNRS-Université Bordeaux Segalen, INRA Bordeaux Aquitaine BP81, Université de Bordeaux, 33 883 Villenave d’Ornon Cedex, France Eric Testet, Laboratoire de Biogenèse Membranaire, UMR 5200 CNRS-Université Bordeaux Segalen, INRA Bordeaux Aquitaine BP81, Université de Bordeaux, 33 883 Villenave d’Ornon Cedex, France Jean-Marie Schmitter, Chimie Biologie des Membranes et Nanoobjets CBMN—UMR 5248 Centre de Génomique Fonctionnelle Université Bordeaux 2, Université de Bordeaux, 146, rue Léo Saignat, 33076 Bordeaux cedex, France Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    This review covers applications of pristine and functionalized single-wall carbon nanotubes (SWCNTs) in nano-medicine, cultural heritage, and biosensors. The physicochemical properties of these engineered nanoparticles are similar to those of ultrafine components of airborne pollution (UF) and might have similar adverse effects. UF may impair cardiovascular autonomic control (inducing a high-risk condition for adverse cardiovascular effects), cause mammalian embryo toxicity, and increase geno-cytotoxic risk. SWCNTs coated with a biopolymer, for example polyethylenimine (PEI), become extremely biocompatible, hence are useful for in-vivo and in-vitro drug delivery and gene transfection. It is also possible to successfully immobilize a human enteric virus on PEI/SWCNT composites, suggesting application as a carrier in non-permissive media. The effectiveness of carbon nanostructured materials in the cleaning, restoration, and consolidation of deteriorated historical surfaces has been widely shown by the use of carbon nanomicelles to remove black dendritic crust from stone surfaces. The nanomicelles, here, have the twofold role of delivery and controlled release of the cleaning agents. The high biocompatibility of functionalized SWCNTs with enzymes and proteins is a fundamental feature used in the assembly of electrochemical biosensors. In particular, a third-generation protoporphyrin IX-based biosensor has been assembled for amperometric detection of nitrite, an environmental pollutant involved in the biodeterioration and black encrustation of historical surfaces. Content Type Journal Article Category Review Pages 1-15 DOI 10.1007/s00216-012-6351-6 Authors F. Valentini, Dipartimento di Scienze e Tecnologie Chimiche, II Università Degli Studi di Roma Tor Vergata, via della Ricerca Scientifica 1, 00133 Roma, Italy M. Carbone, Dipartimento di Scienze e Tecnologie Chimiche, II Università Degli Studi di Roma Tor Vergata, via della Ricerca Scientifica 1, 00133 Roma, Italy G. Palleschi, Dipartimento di Scienze e Tecnologie Chimiche, II Università Degli Studi di Roma Tor Vergata, via della Ricerca Scientifica 1, 00133 Roma, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A novel electrochemical method for the sequence-specific detection of double-stranded polymerase chain reaction (PCR) products of PML/RARα fusion gene in acute promyelocytic leukemia (APL) was described in detail. Based on a “sandwich” sensing mode involving a pair of locked nucleic acids probes (capture probe and reporter probe), this DNA sensor exhibited excellent selectivity and specificity. The direct and quantitative analysis of double-stranded complementary was firstly performed by our sensor without the use of alkali, helicase enzymes, or denaturants. Finally, combining PCR technique with electrochemical detection scheme, PCR amplicons (191 bp) of the PML/RARα fusion gene were obtained and rapidly identified with a low detection limit of 79 fmol in the 100-μL hybridization system. The results clearly showed the power of sensor as a promising tool for the sensitive, specific, and portable detection of APL and other diseases. Content Type Journal Article Category Technical Note Pages 1-6 DOI 10.1007/s00216-012-6477-6 Authors Yun Lei, Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350004 China Mei-juan Feng, Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350004 China Kun Wang, Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350004 China Li-qing Lin, Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350004 China Yuan-zhong Chen, Fujian Institute of Hematology, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, 350000 China Xin-hua Lin, Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350004 China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    We have developed a simple and sensitive method for the simultaneous determination of testosterone (TES), cortisol (CRT), and dehydroepiandrosterone (DHEA) in saliva by automated online in-tube solid-phase microextraction (SPME) coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS) using a Discovery HS F5 column. The optimum in-tube SPME conditions were 25 draw/eject cycles of 40 μL of sample at a flow rate of 200 μL/min using a Supel-Q PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. The in-tube SPME LC–MS/MS method showed good linearity with correlation coefficients r  ≥ 0.9998 for TES, CRT, and DHEA using their respective stable isotope-labeled internal standards. The intra-day and inter-day precisions (relative standard deviations) were below 4.9 and 8.5 % ( n  = 5), respectively. This method was successfully utilized to analyze TES, CRT, and DHEA in saliva samples without any other pretreatment or interference peaks, and the quantification limits (S/N = 10) of TES, CRT and DHEA were about 0.01, 0.03 and 0.29 ng/mL saliva, respectively. The recoveries of these compounds spiked into saliva samples were each above 94 %. This method was applied to analyze changes in salivary TES, CRT, and DHEA levels resulting from stress and fatigue load. Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s00216-012-6479-4 Authors Hiroyuki Kataoka, School of Pharmacy, Shujitsu University, Nishigawara, Okayama, 703-8516 Japan Kentaro Ehara, School of Pharmacy, Shujitsu University, Nishigawara, Okayama, 703-8516 Japan Rie Yasuhara, School of Pharmacy, Shujitsu University, Nishigawara, Okayama, 703-8516 Japan Keita Saito, School of Pharmacy, Shujitsu University, Nishigawara, Okayama, 703-8516 Japan Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A simple, sensitive, and selective liquid chromatography/tandem mass spectrometry method was validated for the identification and quantification of mavoglurant (AFQ056) in human plasma. The chromatographic separation was performed using a Cosmosil 5 C18 (150 × 4.6 mm, 5 μm) column at 40 ± 0.5 °C with a mobile phase consisting of acetic acid in water (0.1 %, v / v )/methanol (10:90, v / v ) with a flow rate of 1.0 mL/min followed by quantification with tandem mass spectrometry, operating with electrospray ionization in positive ion mode and applying multiple reaction monitoring. The validated method described in this paper presents high absolute recovery with precision and accuracy meeting the acceptance criteria. The method was precise and accurate for 2- and 10-fold dilution of samples. The method was validated using sodium heparin as specific anticoagulant, and the anticoagulant effect was tested by lithium heparin and K 3 EDTA. The method was successfully cross-validated between two bioanalytical sites. The method was specific for mavoglurant within the given criteria for acceptance (apparent peak area at the retention time of mavoglurant in zero samples was less than 20 % compared with the mean peak area at LLOQ) in human plasma. The method was fully validated for the quantitative determination of mavoglurant in human plasma between the range of 2.00 and 2,500 ng/mL. Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-6456-y Authors Annamaria Jakab, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma AG., Fabrikstrasse 14, 3.02, 4056 Basel, Switzerland Serge Winter, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056 Basel, Switzerland Marc Raccuglia, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056 Basel, Switzerland Frank Picard, Bioanalytics Division, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056 Basel, Switzerland Swati Dumitras, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056 Basel, Switzerland Ralph Woessner, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056 Basel, Switzerland Sanket Mistry, Veeda Clinical Research Pvt. Ltd, Shivalik Plaza-A, Near I.I.M., Ambawadi, Ahmedabad, 380015 India Jayraj Chudasama, Veeda Clinical Research Pvt. Ltd, Shivalik Plaza-A, Near I.I.M., Ambawadi, Ahmedabad, 380015 India Swati Guttikar, Veeda Clinical Research Pvt. Ltd, Shivalik Plaza-A, Near I.I.M., Ambawadi, Ahmedabad, 380015 India Olivier Kretz, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056 Basel, Switzerland Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Thanks to reviewers in 2012 Content Type Journal Article Category Acknowledgement to Referees Pages 1-12 DOI 10.1007/s00216-012-6438-0 Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    The characterization of the organic components in a complex, multilayered paint structure is fundamental for studying painting techniques and for authentication and restoration purposes. Proteinaceous materials, such as animal glue, are of particular importance since they are widely used as binders, adhesives and for gilding. Even though proteins are usually detected by chromatographic and proteomic techniques, immunological methods represent an alternative powerful approach to protein analysis thanks to the high specificity of antigen–antibody reactions. Our previous studies demonstrated that ovalbumin and casein could be localized in paint cross-sections with high sensitivity and good spatial resolution (i.e. within the single painting layers) by using chemiluminescent (CL) immunochemical microscope imaging. In the present research work, we describe for the first time the immunolocalization of collagen (the main protein of animal glue) in paint cross-sections by CL imaging microscopy. Two different analytical protocols have been developed, allowing either the detection of collagen or the simultaneous detection of collagen and ovalbumin in the same paint sample. The assays were used to detect collagen and ovalbumin in cross-sections from model samples and historical paintings (a wall painting dated to 1773–1774 and a painted wood panel of the Renaissance period) in order to achieve information on paint techniques and past restoration interventions. Figure  Left Reflected light image of a cross-section of a sample taken from a Renaissance painted wood panel. Right Localization of the proteins collagen (from animal glue) and ovalbumin in a painting cross-section assessed by multiplexed chemiluminescence immunochemical imaging (the chemiluminescent signals corresponding to collagen and ovalbumin are displayed in shades of blue and red , respectively) Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s00216-012-6463-z Authors G. Sciutto, Microchemistry and Microscopy Art Diagnostic Laboratory M2ADL, University of Bologna, Ravenna Campus, 48121 Ravenna, Italy L. S. Dolci, Health Sciences and Technologies (HST) Interdepartmental Center for Industrial Research, University of Bologna, 40126 Bologna, Italy M. Guardigli, Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, Italy M. Zangheri, Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, Italy S. Prati, Microchemistry and Microscopy Art Diagnostic Laboratory M2ADL, University of Bologna, Ravenna Campus, 48121 Ravenna, Italy R. Mazzeo, Microchemistry and Microscopy Art Diagnostic Laboratory M2ADL, University of Bologna, Ravenna Campus, 48121 Ravenna, Italy A. Roda, Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Sample preparation is an important step for the determination of phenolic compounds in biological samples. Different extraction methods have been tested to determine phenolic compounds and their metabolites in plasma by nano-liquid chromatography coupled to electrospray ionisation-time-of-flight mass spectrometry (nanoLC-ESI-TOF-MS). The sample treatment optimisation was performed using commercial foetal bovine serum spiked with representative phenolic standards, namely naringenin, luteolin, verbascoside, apigenin, rutin, syringic acid and catechin. Different protein-precipitation conditions were evaluated as well as enzymatic digestion with trypsin and solid-phase extraction using different phases such as C-18, ABN and ENV+, working at different pH values. The optimum extraction procedure consisted of a previous protein-precipitation step using HCl 200 mmol/L in methanol for 2.5 h at 50 °C followed by a solid-phase extraction using C-18 cartridges at pH 2.5. This procedure was finally applied to the plasma of rats overfed with a phenolic-rich Lippia citriodora extract. These samples were analysed by nanoLC-ESI-TOF-MS, enabling the identification of five compounds previously found in the administered L. citriodora extract and one metabolite. Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s00216-012-6402-z Authors R. Quirantes-Piné, Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avd. Fuentenueva s/n, 18071 Granada, Spain V. Verardo, Department of Food Science, University of Bologna, Piazza Goidanich 60, 47521 Cesena, FC, Italy D. Arráez-Román, Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avd. Fuentenueva s/n, 18071 Granada, Spain S. Fernández-Arroyo, Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avd. Fuentenueva s/n, 18071 Granada, Spain V. Micol, Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Avenida de la Universidad s/n, 03202 Elche, Alicante, Spain M. F. Caboni, Department of Food Science, University of Bologna, Piazza Goidanich 60, 47521 Cesena, FC, Italy A. Segura-Carretero, Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avd. Fuentenueva s/n, 18071 Granada, Spain A. Fernández-Gutiérrez, Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avd. Fuentenueva s/n, 18071 Granada, Spain Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Specific and sensitive analysis to reveal and monitor the wide variety of chemical contaminants polluting all environment compartments, feed, and food is urgently required because of the increasing attention devoted to the environment and health protection. Our research group has been involved in monitoring the presence and distribution of agrochemicals by monitoring beehives distributed throughout the area studied. Honeybees have been used both as biosensors, because the pesticides affect their viability, and as “contaminant collectors” for all environmental pollutants. We focused our research on the development of analytical procedures able to reveal and quantify pesticides in different samples but with a special attention to the complex honeybee matrix. Specific extraction and purification procedures have been developed and some are still under optimization. The analytes of interest were determined by gas or liquid chromatographic methods and by compound-specific or group-specific immunoassays in the ELISA format, the analytical performance of which was improved by introducing luminescence detection. The range of chemiluminescent immunoassays developed was extended to include the determination of completely different pollutants, for example explosives, volatile organic compounds (including benzene, toluene, ethylbenzene, xylenes), and components of plastics, for example bisphenol A. An easier and portable format, a lateral flow immunoassay (LFIA) was added to the ELISA format to increase application flexibility in these assays. Aspects of the novelty, the specific characteristics, the analytical performance, and possible future development of the different chromatographic and immunological methods are described and discussed. Fig  Map of a territory monitored by using honeybees, showing the areas covered by each beehive station (circles) and thedifferent agricultural products included in it (different colours). Content Type Journal Article Category Review Pages 1-17 DOI 10.1007/s00216-012-6443-3 Authors S. Girotti, Department of Metallurgic Sciences, Electrochemistry and Chemical Techniques, University of Bologna, Via S. Donato 15, 40127 Bologna, Italy S. Ghini, Department of Metallurgic Sciences, Electrochemistry and Chemical Techniques, University of Bologna, Via S. Donato 15, 40127 Bologna, Italy E. Maiolini, Department of Metallurgic Sciences, Electrochemistry and Chemical Techniques, University of Bologna, Via S. Donato 15, 40127 Bologna, Italy L. Bolelli, Department of Metallurgic Sciences, Electrochemistry and Chemical Techniques, University of Bologna, Via S. Donato 15, 40127 Bologna, Italy E. N. Ferri, Department of Metallurgic Sciences, Electrochemistry and Chemical Techniques, University of Bologna, Via S. Donato 15, 40127 Bologna, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    A high analytical sensitivity in ultraviolet matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is only achieved if the laser wavelength corresponds to a high optical absorption of the matrix. Laser fluence and the physicochemical properties of the compounds, e.g., the proton affinity, also influence analytical sensitivity significantly. In combination, these parameters determine the amount of material ejected per laser pulse and the ion yield, i.e., the fraction of ionized biomolecules. Here, we recorded peptide ion signal intensities as a function of these parameters. Three cinnamic acid matrices were investigated: α-cyano-4-hydroxycinnamic acid, α-cyano-4-chlorocinnamic acid, and α-cyano-2,4-difluorocinnamic acid. In addition, 2,5-dihydroxybenzoic acid was used in comparison experiments. Ion signal intensities “per laser shot” and integrated ion signal intensities were acquired over 900 consecutive laser pulses applied on distinct positions on the dried-droplet sample preparations. With respect to laser wavelength, the two standard MALDI wavelengths of 337/355 nm were investigated. Also, 305 or 320 nm was selected to account for the blue-shifted absorption profiles of the halogenated derivatives. Maximal peptide ion intensities were obtained if the laser wavelength fell within the peak of the absorption profile of the compound and for fluences two to three times the corresponding ion detection threshold. The results indicate ways for improving the analytical sensitivity in MALDI-MS, and in particular for MALDI-MS imaging applications where a limited amount of material is available per irradiated pixel. Content Type Journal Article Category Paper in Forefront Pages 1-8 DOI 10.1007/s00216-012-6478-5 Authors Marcel Wiegelmann, Institute for Hygiene, University of Münster, Robert-Koch-Str. 41, 48149 Münster, Germany Jens Soltwisch, Institute for Hygiene, University of Münster, Robert-Koch-Str. 41, 48149 Münster, Germany Thorsten W. Jaskolla, Institute for Hygiene, University of Münster, Robert-Koch-Str. 41, 48149 Münster, Germany Klaus Dreisewerd, Institute for Hygiene, University of Münster, Robert-Koch-Str. 41, 48149 Münster, Germany Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: Purpose   To explore the impact of UDP-glucuronosyltransferase polymorphisms ( UGT1A9-118(dT) 9/10 , UGT1A9 CI399T , UGT1A9 C-440T and UGT2B7 G211T ) on the pharmacokinetics of mycophenolic acid (MPA) in healthy Chinese volunteers. Methods   We recruited ten healthy volunteers with no polymorphisms (control group), 11 homozygotes of mutants UGT1A9 CI399T and UGT1A9-118(dT) 9/10 , ten heterozygotes of UGT1A9 C440T and seven carriers of UGT2B7 211T from a total of 518 healthy Chinese volunteers. All the volunteers were orally administered a single dose of 1.5 g mycophenolate mofetil (MMF) after an overnight fast. Plasma was then collected 72 h after MMF administration. MPA, MPA-7-O-glucuronide (MPAG) and its acylglucuronide (AcMPAG) were detected by ultra-pressure liquid chromatography with UV detection. Results   Compared with the control group, the UGT1A9 CI399T and UGT1A9-118(dT) 9/10 mutant homozygotes had higher MPAG plasma concentrations. Subjects with UGT1A9-440TC had enhanced MPA exposure while carriers of UGT2B7 211T had higher concentrations of the toxic metabolite, AcMPAG. Conclusions   The current results indicate that UGT1A9 and UGT2B7 genotypes could significantly alter MPA pharmacokinetics in healthy Chinese volunteers after a single oral dose of MMF. Content Type Journal Article Category Pharmacokinetics and Disposition Pages 1-7 DOI 10.1007/s00228-012-1409-0 Authors Dong Guo, Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China Liang-Fang Pang, Pharmacy Department, Donghu Hospital, Wuhan, 430079 China Yang Han, Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China Hong Yang, Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China Guo Wang, Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China Zhi-rong Tan, Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China Wei Zhang, Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China Hong-Hao Zhou, Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970

Description:    This critical review focuses on inductively coupled plasma mass spectrometry (ICP-MS) based applications for isotope abundance ratio measurements in various clinical samples relevant to monitoring occupational or environmental exposure, human provenancing and reconstruction of migration pathways as well as metabolic research. It starts with a brief overview of recent advances in ICP-MS instrumentation, followed by selected examples that cover the fields of accurate analyte quantification using isotope dilution, tracer studies in nutrition and toxicology, and areas relying upon natural or man-made variations in isotope abundance ratios (Pb, Sr, actinides and stable heavy elements). Finally, some suggestions on future developments in the field are provided. Content Type Journal Article Category Review Pages 1-13 DOI 10.1007/s00216-012-6457-x Authors Ilia Rodushkin, ALS Scandinavia AB, Aurorum 10, 977 75 Luleå, Sweden Emma Engström, ALS Scandinavia AB, Aurorum 10, 977 75 Luleå, Sweden Douglas C. Baxter, ALS Scandinavia AB, Aurorum 10, 977 75 Luleå, Sweden Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Cardiovascular diseases are the world’s number one cause of death, accounting for 17.1 million deaths a year. New high-resolution molecular and structural imaging strategies are needed to understand underlying pathophysiological mechanism. The aim of our study is (1) to provide a molecular basis of the heart animal model through the local identification of biomolecules by mass spectrometry imaging (MSI) (three-dimensional (3D) molecular reconstruction), (2) to perform a cross-species validation of secondary ion mass spectrometry (SIMS)-based cardiovascular molecular imaging, and (3) to demonstrate potential clinical relevance by the application of this innovative methodology to human heart specimens. We investigated a MSI approach using SIMS on the major areas of a rat and mouse heart: the pericardium, the myocardium, the endocardium, valves, and the great vessels. While several structures of the heart can be observed in individual two-dimensional sections analyzed by metal-assisted SIMS imaging, a full view of these structures in the total heart volume can be achieved only through the construction of the 3D heart model. The images of 3D reconstruction of the rat heart show a highly complementary localization between Na + , K + , and two ions at m/z 145 and 667. Principal component analysis of the MSI data clearly identified different morphology of the heart by their distinct correlated molecular signatures. The results reported here represent the first 3D molecular reconstruction of rat heart by SIMS imaging. Figure  Workflow of the 3D reconstruction. A Tissue section, B gold deposition is done by sputter coating, C , C1 SIMS-ToF mass analyzer, C , C2 mass spectral peaks, C , C3 datacube images; D , E Reconstruction of the heart showing 3D-spatial distributions of three different ions 145 m/z ( red ), 23 m/z ( green ), and 39 m/z ( blue ); F coregistration of 40 individual MS imaging Content Type Journal Article Category Original Paper Pages 1-12 DOI 10.1007/s00216-012-6451-3 Authors Lara Fornai, Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Gabelli 61, 35121 Padua, Italy Annalisa Angelini, Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Gabelli 61, 35121 Padua, Italy Ivo Klinkert, FOM-AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands Frans Giskes, FOM-AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands Andras Kiss, FOM-AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands Gert Eijkel, FOM-AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands Erika A. Amstalden-van Hove, FOM-AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands Leendert A. Klerk, FOM-AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands Marny Fedrigo, Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Gabelli 61, 35121 Padua, Italy Giuseppe Pieraccini, CISM Mass Spectrometry Centre, Viale Pieraccini 6 University of Florence, 50139 Florence, Italy Gloriano Moneti, CISM Mass Spectrometry Centre, Viale Pieraccini 6 University of Florence, 50139 Florence, Italy Marialuisa Valente, Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Gabelli 61, 35121 Padua, Italy Gaetano Thiene, Cardiovascular Pathology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Via Gabelli 61, 35121 Padua, Italy Ron M. A. Heeren, FOM-AMOLF, Science Park 104, 1098 XG, Amsterdam, The Netherlands Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Chemiluminescence (CL) emission from luminol–tetrachloroaurate ([AuCl 4 ] − ) system studied in presence of monosaccharide sugars such as glucose and fructose was investigated on a microfluidic chip fabricated by the soft lithography technique. CL emission from the luminol–[AuCl 4 ] − system at 430 nm was intensified remarkably by the catalytic activity of glucose and fructose at room temperature. Under optimized conditions, the CL emission intensity of the system was found to be linearly related to the concentration of the sugars. Based on this observation, nonenzymatic determination of total sugar (glucose, fructose, or hydrolyzable sucrose) was performed in a rapid and sensitive analytical method. The results revealed that the linearity ranged from 9 to 1,750 μM for glucose and 80 to 1,750 μM for fructose, with a limit of detection of 0.65 and 0.69 μM, respectively. The relative standard deviations determined at 250 μM based on six repetitive injections were 1.13 and 1.15 % for glucose and fructose, respectively. The developed method was successfully applied for determination of the total sugar concentration in food and beverages. Figure  Schematic diagram and plausible chemical reaction scheme of microfluidic chip based enzymless determination of total sugar concentration. ( a ) CL emission for reaction between luminol and [AuCl 4 ]- in absence of sugar; ( b ) Enhanced CL emission when reaction mixture of reducing sugar and [AuCl 4 ]- merge with the luminol stream in the chip. SP-1, SP-2, and SP-3 represent the syringe pumps that deliver H 2 O/Sugar sample, [AuCl 4 ]- and luminol solution, respectively, to the chip. M first mixing zone; D mixing and detection zone, W waste out Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-6429-1 Authors Al-Mahmnur Alam, Department of Chemistry, Kyungpook National University, Daegu, 702-701 South Korea Mohammad Kamruzzaman, Department of Chemistry, Kyungpook National University, Daegu, 702-701 South Korea Trung-Dung Dang, School of Mechanical Engineering, Yeungnam University, Gyeongsan, 712-749 South Korea Sang Hak Lee, Department of Chemistry, Kyungpook National University, Daegu, 702-701 South Korea Young Ho Kim, Research Institute of Advanced Energy Technology, Kyungpook National University, Daegu, 702-701 South Korea Gyu-Man Kim, School of Mechanical Engineering, Kyungpook National University, Daegu, 702-701 South Korea Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Polymeric thin films have been awakening continuous and growing interest for application in nanotechnology. For such applications, the assessment of their (nano)mechanical properties is a key issue, since they may dramatically vary between the bulk and the thin film state, even for the same polymer. Therefore, techniques are required for the in situ characterization of mechanical properties of thin films that must be nondestructive or only minimally destructive. Also, they must also be able to probe nanometer-thick ultrathin films and layers and capable of imaging the mechanical properties of the sample with nanometer lateral resolution, since, for instance, at these scales blends or copolymers are not uniform, their phases being separated. Atomic force microscopy (AFM) has been proposed as a tool for the development of a number of techniques that match such requirements. In this review, we describe the state of the art of the main AFM-based methods for qualitative and quantitative single-point measurements and imaging of mechanical properties of polymeric thin films, illustrating their specific merits and limitations. Content Type Journal Article Category Review Pages 1-16 DOI 10.1007/s00216-012-6419-3 Authors Daniele Passeri, Department of Basic and Applied Sciences for Engineering, University of Rome Sapienza, Via A. Scarpa 16, 00161 Rome, Italy Marco Rossi, Department of Basic and Applied Sciences for Engineering, University of Rome Sapienza, Via A. Scarpa 16, 00161 Rome, Italy Emanuela Tamburri, Department of Chemical Sciences and Technologies, University of Rome Tor Vergata and Micro and Nano-structured Systems Laboratory (MINASlab), Via della Ricerca Scientifica, 00133 Rome, Italy Maria Letizia Terranova, Department of Chemical Sciences and Technologies, University of Rome Tor Vergata and Micro and Nano-structured Systems Laboratory (MINASlab), Via della Ricerca Scientifica, 00133 Rome, Italy Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Laser desorption postionization mass spectrometry (LDPI-MS) imaging is demonstrated with a 10.5 eV photon energy source for analysis and imaging of small endogenous molecules within intact biofilms. Biofilm consortia comprised of a synthetic Escherichia coli K12 coculture engineered for syntrophic metabolite exchange are grown on membranes and then used to test LDPI-MS analysis and imaging. Both E. coli strains displayed many similar peaks in LDPI-MS up to m/z 650, although some observed differences in peak intensities were consistent with the appearance of byproducts preferentially expressed by one strain. The relatively low mass resolution and accuracy of this specific LDPI-MS instrument prevented definitive assignment of species to peaks, but strategies are discussed to overcome this shortcoming. The results are also discussed in terms of desorption and ionization issues related to the use of 10.5 eV single-photon ionization, with control experiments providing additional mechanistic information. Finally, 10.5 eV LDPI-MS was able to collect ion images from intact, electrically insulating biofilms at ∼100 μm spatial resolution. Spatial resolution of ∼20 μm was possible, although a relatively long acquisition time resulted from the 10 Hz repetition rate of the single-photon ionization source. Figure  Neutral species laser desorbed from cocultured biofilms undergo single photon ionization by VUV radiation and resultant ions are detected by time-of-flight mass spectrometry Content Type Journal Article Category Original Paper Pages 1-9 DOI 10.1007/s00216-012-6454-0 Authors Chhavi Bhardwaj, Department of Chemistry, MC 111, University of Illinois at Chicago, Chicago, IL 60607-7061, USA Jerry F. Moore, MassThink, LLC, 500 E. Ogden Avenue Suite 200, Naperville, IL 60563, USA Yang Cui, Department of Chemistry, MC 111, University of Illinois at Chicago, Chicago, IL 60607-7061, USA Gerald L. Gasper, Department of Chemistry, MC 111, University of Illinois at Chicago, Chicago, IL 60607-7061, USA Hans C. Bernstein, Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA Ross P. Carlson, Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA Luke Hanley, Department of Chemistry, MC 111, University of Illinois at Chicago, Chicago, IL 60607-7061, USA Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Intercellular Ca 2+ waves are propagation of Ca 2+ transients among cells that could be initiated by chemical stimulation. Current methods for analyzing intercellular Ca 2+ waves are difficult to realize localized chemical stimulations upon the target cell without interfering with adjacent contacting cells. In this paper, a simple and flexible microfluidic method was developed for investigating the intercellular communication of Ca 2+ signals. A cross-patterned microfluidic chip was designed and fabricated with polydimethylsiloxane as the structural material. Localized chemical stimulation was achieved by a new strategy based on hydrodynamic gating technique. Clusters of target cells were seeded at the location within 300 μm downstream of the intersection of the cross-shaped microchannel. Confined lateral molecular diffusion largely minimized the interference from diffusion-induced stimulation of adjacent cells. Localized stimulation of the target cell with adenosine 5′-triphosphate successfully induced the propagation of intercellular Ca 2+ waves among a population of adjacent contacting cells. Further inhibition studies verified that the propagation of calcium signals among NIH-3 T3 cells was dependent on direct cytosolic transfer via gap junctions. The developed microfluidic method provides a versatile platform for investigating the dynamics of intercellular communications. Content Type Journal Article Category Original Paper Pages 1-8 DOI 10.1007/s00216-012-6447-z Authors Peng Chen, Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics–Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China Pu Chen, Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics–Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China Xiaojun Feng, Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics–Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China Wei Du, Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics–Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China Bi-Feng Liu, Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics–Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description:    Meglumine antimonate is the active of Glucantime® used for the treatment of leishmaniasis, a tropical disease caused by parasitic protozoa, and it is estimated that 12 million people worldwide are affected. This drug mainly contains Sb(V) under the form of an organic complex with N -methylglucamine (NMG). During the synthesis of this molecule, traces of Sb(III) may be present, also probably complexed. Due to the fact that Sb(III) is considered more toxic than Sb(V), it is important to evaluate the Sb(III) concentration in the drug samples. In the literature, very different concentrations for residual concentrations of Sb(III) in the drug ampoules are found. Therefore, to have a true insight of antimony speciation, two independent analytical methods were developed in this work. We used an anion exchange method coupled with inductively coupled plasma mass spectrometry (ICP-MS) which was cross-referenced with an electrochemistry method (differential pulse polarography (DPP)) that could be used for routine analysis on the production site. To obtain Sb species in detectable forms, the complexes between Sb species and NMG need to be broken. This was obtained by diluting samples in hydrochloric acid in deaerated conditions to avoid Sb redox reactions. For the two analytical methods, the HCl concentration was optimized to obtain simultaneously a complete destruction of the complexes as well as limited redox reactions for Sb(V) and Sb(III) released species. For high-performance liquid chromatography (HPLC)-ICP-MS, a dilution with 5 M HCl gives the better results. The side reaction is an oxidation of Sb(III) which can be limited by the removal of oxygen. When DPP is used, the major problem is the reduction of Sb(V) which is present in high amount in the samples. Working with 0.6 M HCl allows this problem to be minimized. When applied to different lots of Glucantime®, Sb(III) concentration values are in good agreement for the two analytical methods, with, for HPLC-ICP-MS, the advantage of the simultaneous detection of both Sb redox species. Content Type Journal Article Category Original Paper Pages 1-10 DOI 10.1007/s00216-012-6427-3 Authors F. Séby, Ultratraces Analyses Aquitaine, Hélioparc Pau-Pyrénées, 2, avenue du Président Angot, 64053 Pau Cedex 9, France C. Gleyzes, Ultratraces Analyses Aquitaine, Hélioparc Pau-Pyrénées, 2, avenue du Président Angot, 64053 Pau Cedex 9, France O. Grosso, SANOFI, 20 avenue Raymond Aron, 92165 Antony, France B. Plau, SANOFI, 20 avenue Raymond Aron, 92165 Antony, France O. F. X. Donard, Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, IPREM UMR 5254, CNRS, Université de Pau et des Pays de l’Adour, Hélioparc Pau-Pyrénées, 2, avenue du Président Angot, 64053 Pau Cedex 9, France Journal Analytical and Bioanalytical Chemistry Online ISSN 1618-2650 Print ISSN 1618-2642

Description: ACE inhibitors and ribavirin-associated cough: a common undefined predisposing factor? Content Type Journal Article Category Letter to the Editors Pages 1-3 DOI 10.1007/s00228-012-1397-0 Authors Laura Milazzo, Department of Infectious Diseases, Luigi Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy Dario Cattaneo, Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Milan, Italy Stefania Cheli, Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Milan, Italy Laurenzia Ferraris, Department of Infectious Diseases, Luigi Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy Elisa Colella, Department of Infectious Diseases, Luigi Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy Emilio Clementi, Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Milan, Italy Cristina Gervasoni, Department of Infectious Diseases, Luigi Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy Journal European Journal of Clinical Pharmacology Online ISSN 1432-1041 Print ISSN 0031-6970