title: Determination of lansoprazole enantiomers in dog plasma by column-switching liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study.
abstract: Lansoprazole, a selective proton pump inhibitor, has a chiral benzimidazole sulfoxide structure and is used for the treatment of gastric acid hypersecretory related diseases. To investigate its stereoselective pharmacokinetics, a column-switching liquid chromatography with tandem mass spectrometry method was developed for the determination of lansoprazole enantiomers in dog plasma using (+)-pantoprazole as an internal standard. After a simple protein precipitation procedure with acetonitrile, matrix components left behind after sample preparation were further eliminated from the sample by reversed-phase chromatography on a C18 column. The fluent was fed to a chiral column for the separation of lansoprazole enantiomers. Baseline separation of lansoprazole enantiomers was achieved on a Chiralcel OZ-RH column using acetonitrile/0.1% formic acid in water (35:65, v/v) as the mobile phase at 40°C. The linearity of the calibration curves ranged from 3 to 800 ng/mL for each enantiomer. Intra- and inter-day precisions ranged from 2.1 to 7.3% with an accuracy of ±1.7% for (+)-lansoprazole, and from 1.6 to 6.9% with an accuracy of ±3.5% for (-)-lansoprazole, respectively. The validated method was successfully applied for the stereoselective pharmacokinetic study of lansoprazole in beagle dog after intravenous infusion.
authors.affiliation: School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Research Center for Drug Metabolism, Jilin University, Changchun, P.R. China.|School of Pharmaceutical Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Yantong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Southeast Environmental Research Center, Florida International University, North Miami, FL, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Research Center for Drug Metabolism, Jilin University, Changchun, P.R. China.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D004867:Equipment Design; D005744:Gastric Acid / Q000737:chemistry; D064747:Lansoprazole / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D057230:Limit of Detection; D010949:Plasma; D011786:Quality Control; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D064747:Lansoprazole
keywords: Column-switching procedure; Enantioselective pharmacokinetics; Lansoprazole; Liquid chromatography with tandem mass spectrometry