title: Determination of rabeprazole enantiomers in dog plasma by supercritical fluid chromatography tandem mass spectrometry and its application to a pharmacokinetic study.
abstract: Rabeprazole is a novel benzimidazole proton pump inhibitor used for the treatment of gastrointestinal disorders. It is a chiral molecule that gives rise to the possibility of stereoselective pharmacokinetics. To investigate this phenomenon, a rapid and sensitive chiral assay based on supercritical fluid chromatography tandem mass spectrometry was developed and applied to the determination of (R)-rabeprazole and (S)-rabeprazole in dog plasma. Sample preparation involved protein precipitation with acetonitrile after the addition of (R)-lansoprazole as internal standard. Baseline separation of enantiomers in 4.5 min was achieved on an Acquity UPC2system using an ACQUITY UPC2Trefoil CEL2 column maintained at 60°C and a mobile phase consisting of methanol/CO2(30:70, v/v) delivered at 2.5 mL/min. Detection was achieved by multiple reaction monitoring of the transitions at m/z 360.0→242.2 (rabeprazole) and 370.3→252.0 (internal standard) in the positive ion mode. The assay was linear in the range of 1-1000 ng/mL and free of matrix effects. Intra- and interday precisions were less than 10.0% with accuracy in the range of -2.6 to 3.1%. The method was successfully applied to a pharmacokinetic study of rabeprazole enantiomers after administration of a single oral dose of 10 mg racemate to beagle dogs.
authors.affiliation: College of Life Science, Jilin University, Changchun, P. R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Su
authors.affiliation: College of Life Science, Jilin University, Changchun, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Life Science, Jilin University, Changchun, P. R. China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Fawcett
authors.affiliation: Department of Technology, Waters Corporation, Shanghai, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Life Science, Jilin University, Changchun, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Life Science, Jilin University, Changchun, P. R. China.|Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, P. R. China.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D025924:Chromatography, Supercritical Fluid; D004285:Dogs; D010949:Plasma / Q000737:chemistry*; D064750:Rabeprazole / Q000097:blood*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D064750:Rabeprazole
keywords: chiral separation; mass spectrometry; rabeprazole; stereoselective pharmacokinetics; supercritical fluid chromatography