ISSN:
1573-904X
Keywords:
partition coefficient
;
log P
;
log D
;
high throughput
;
physicochemical
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. To present an increased throughput automated shake-flask method for the direct determination of the partition coefficients of solutes between octan-1-ol and buffer. Method. The traditional shake-flask method has been transferred onto 96-well plate technology and a robotic liquid handler has been used for sample preparation. A custom programmed Gilson auto- sampler samples the organic and aqueous phases directly from the plate, circumventing the need for any manual separation. Analyses are performed by reverse phase high performance liquid chromatography (RP-HPLC). Generic fast gradient RP-HPLC conditions are used to eliminate chromatographic method development time and reduce analysis time. Results. A full validation of the automated method is presented for a range of compounds with log D values between −2 and 4. Conclusions. The advantages and limitations of this direct measurement method are discussed. The use of this methodology provides a means to rapidly assess log D values for large compound arrays.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007546905874
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