title: Chiral assay of omeprazole and metabolites and its application to a pharmacokinetics related to CYP2C19 genotypes.
abstract: Studies investigating the relationship between CYP2C19 genotype and the stereoselective metabolism of omeprazole have not been reported. In the present study, we developed a simple and sensitive analytical method based on column switching reversed phase high-performance liquid chromatography (HPLC) with UV detection to determine the concentrations of (R)- and (S)-omeprazole and of its principal metabolites, (R)- and (S)-5-hydroxyomeprazole, and the non-chiral, omeprazole sulfone, in human plasma. Sample preparation involved liquid-liquid extraction with diethyl ether:dichloromethane (60:40, v/v) followed by clean-up on a TSK BSA-ODS/S column (5 μm, 10 mm × 4.6mm i.d.) using phosphate buffer:acetonitrile (97:3, v/v, pH 6.4). After column switching, separation was performed on a Shiseido CD-ph chiral column (5 μm, 150 mm × 4.6mm i.d.) using phosphate buffer:methanol (45:55, v/v, pH 5.0) as mobile phase. The limit of quantitation (LOQ) was 5 ng/mL for all analytes with intra- and inter-day precisions (as coefficient of variation) of <9.5% and <9.6%, respectively for all analytes. The present method was successfully applied to a chiral pharmacokinetic study of omeprazole in human volunteers with different CYP2C19 genotypes. The results show that the formation of (R)-5-hydroxyomeprazole gives the best correlation with CYP2C19 genotype.
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-Cho, Okinawa 903-0215, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shiohira
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tateishi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000032:analysis / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D065731:Cytochrome P-450 CYP2C19; D005838:Genotype; D006801:Humans; D009853:Omeprazole / Q000097:blood* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C049963:5-hydroxymethylomeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole