title: Application of a liquid chromatographic/tandem mass spectrometric method to a urinary excretion study of rabeprazole and two of its metabolites in healthy human urine.
abstract: To study urinary excretion properties of rabeprazole and two of its metabolites, i.e. rabeprazole thioether and desmethyl rabeprazole thioether in human urine, a sensitive, selective, accurate and precise method for the quantification of rabeprazole and two of its metabolites using a liquid chromatographic/tandem mass spectrometric method has been developed and validated. Starting with a 200 μL urine aliquot, a general sample preparation was performed using protein precipitation with methanol. Analytes were separated on a Dikma Inspire™ C18 column (150 mm × 2.1mm, 5 μm) using a mixture of methanol and aqueous 10mM ammonium acetate buffer containing 0.05% formic acid (55:45, v/v) as mobile phase. Linearity was obtained over the concentration range of 0.1446-96.38 ng/mL, 0.3198-319.8 ng/mL and 0.05160-82.53 ng/mL for rabeprazole, rabeprazole thioether, desmethyl rabeprazole thioether in human urine, respectively. The fully validated method was applied to a urine excretion study of rabeprazole sodium administered as a 30 min intravenous infusion for the first time. The calculated cumulative urinary recovery just reached 0.04745‰, 1.272‰ and 0.1631‰ of dose within 24h post-dose for rabeprazole, rabeprazole thioether, and desmethyl rabeprazole thioether, respectively, after intravenous infusion administration, indicating that rabeprazole and its two main metabolites undergo substantial non-renal elimination in healthy Chinese volunteers.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Pharmacy, General Hospital of Guangzhou Military Command of PLA, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, General Hospital of Guangzhou Military Command of PLA, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: ad_wen@163.com.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China. Electronic address: dinglidl@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D064750:Rabeprazole / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013440:Sulfides / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D013440:Sulfides; C523099:rabeprazole-thioether; D064750:Rabeprazole
keywords: Desmethyl rabeprazole thioether; LC–MS/MS; Pharmacokinetics; Rabeprazole; Rabeprazole thioether