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Chiral separation and pharmacokinetic study of antihistamine drugs.

A significant enantioselective difference between (−)- and (+)-butoconazole existed in the stage of not only pharmacokinetics but also tissue distribution.

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In this study, a specific and sensitive method of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the determination of penconazole enantiomers in rat plasma. The enantioseparation was achieved on a Chiralpak IC column by using acetonitrile/water (80:20, v/v) as the mobile phase. Penconazole enantiomers and internal standard l-lansoprazole (IS) were detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization source. The method was validated over the concentration range of 2.5–250.0 ng mL−1 for penconazole enantiomers. Good linearity was obtained for both enantiomers with correlation coefficients (R) greater than 0.995. The relative error was well within the admissible range of −1.1–3.2%, and relative standard deviation was less than 6.0%. After validation, the established method was successfully applied to a stereoselective toxicokinetic study in female and male rats after oral administration of 50 mg kg−1 racemic penconazole. This is the first experiment regarding the stereospecific toxicokinetic study of penconazole and the bioanalytical approach for its quantitation in vivo.