title: Determination of rabeprazole enantiomers and their metabolites by high-performance liquid chromatography with solid-phase extraction.
abstract: Here, we describe the development of a rapid, simple and sensitive high-performance liquid chromatography (HPLC) method for the simultaneous quantitative determination of rabeprazole enantiomers (1a,b) and their metabolites, rabeprazole-thioether (2) and rabeprazole sulfone (3), in human plasma. Analytes and the internal standard (omeprazole-thioether) were separated using a mobile phase of 0.5 M NaClO4-acetonitrile (6:4, v/v) over a Chiral CD-Ph column. Analysis required only 100 microl of plasma and involved solid-phase extraction with an Oasis HLB cartridge, which gave high recovery (>91.8%) with good selectivity for all analytes. The lower limit of quantification was 5 ng/ml for analytes 1a, 1b and 3 and 10 ng/ml for 2. Linearity of this assay was determined to lie between 5 and 1000 ng/ml for 1a, 1b and 3 and 10 and 1000 ng/ml for 2 (r2>0.982 of the regression line). Inter- and intra-day coefficients of variation were less than 7.8% and accuracies were within 8.4% over the linear range for all analytes. Our results indicate that this method is applicable to the simultaneous monitoring of plasma levels of rabeprazole enantiomers and associated metabolites in human plasma.
authors.affiliation: Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000897:Anti-Ulcer Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D065731:Cytochrome P-450 CYP2C19; D006801:Humans; D007536:Isomerism; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D016030:Kidney Transplantation; D006899:Mixed Function Oxygenases / Q000378:metabolism; D064750:Rabeprazole; D015203:Reproducibility of Results; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D013440:Sulfides; D064750:Rabeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19