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Simultaneous determination of nicotine and its nine metabolites in rat blood utilizing microdialysis coupled with UPLC–tandem mass spectrometry for pharmacokinetic application

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Abstract

To develop a simple and rapid method for the simultaneous determination of nicotine and its nine metabolites in rat blood, an in vivo microdialysis sampling technique coupled with ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was established for quantitation and characterization of the pharmacokinetics of nicotine and its metabolites. Microdialysis probes were inserted into the jugular vein of Sprague Dawley rats, and dialysates were collected after nicotine (0.5 mg/kg, i.p.) administration. Target analytes and corresponding deuterated internal standards were separated on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1. × 150 mm, 1.7 μm) and detected by UPLC–MS/MS under multiple reaction monitoring mode. The limits of quantification for nicotine and its nine metabolites ranged from 0.039 to 0.46 ng/mL. Intra- and inter-day precision and accuracy were well within the predefined limits of acceptability (<11 %). Pharmacokinetic results showed that the mean half-lives of nicotine, cotinine, nornicotine, norcotinine, nicotine-N′-oxide, cotinine-N′-oxide, trans-3′-hydroxy-cotinine, nicotine-N-glucuronide, cotinine-N-glucuronide, and trans-3′-hydroxy-cotinine-O-glucuronide in rat plasma were 63, 291, 175, 440, 251, 451, 322, 341, 488, and 516 min, respectively. The blood concentration-time profiles of nicotine and its nine metabolites indicate that nicotine is rapidly consumed after the administration and subsequently cotinine is generated as the main metabolite; meanwhile, cotinine and other eight minor metabolites exhibit longer retention times in rat body.

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Acknowledgments

This study was supported by NSFC (Grant no. 21307163) and the Presidential Science and Technology Development Foundation of ZTRI, China (No. 412011CA0280).

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Authors and Affiliations

  1. Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou, 450001, China

    Jian Mao, Binbin Lu, Junhui Liu, Guangfeng Hong, Qidong Zhang, Shihao Sun & Jianxun Zhang

  2. School of Life Science, Beijing Institute of Technology, Beijing, 100081, China

    Yan Xu

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  1. Jian Mao
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  2. Yan Xu
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  3. Binbin Lu
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  4. Junhui Liu
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  5. Guangfeng Hong
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  6. Qidong Zhang
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  7. Shihao Sun
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  8. Jianxun Zhang
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Correspondence to Jian Mao or Jianxun Zhang.

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Mao, J., Xu, Y., Lu, B. et al. Simultaneous determination of nicotine and its nine metabolites in rat blood utilizing microdialysis coupled with UPLC–tandem mass spectrometry for pharmacokinetic application. Anal Bioanal Chem 407, 4101–4109 (2015). https://doi.org/10.1007/s00216-015-8643-0

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  • DOI: https://doi.org/10.1007/s00216-015-8643-0

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