title: Determination of pibutidine metabolites in human plasma by LC-MS/MS.
abstract: A novel metabolite-screening procedure for pibutidine. an H2-receptor antagonist, which uses high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS), demonstrated the presence of pibutidine and its four metabolites in plasma from volunteers who received a single dose of pibutidine hydrochloride. In order to quantitatively examine the metabolism of pibutidine, an assay based on LC-MS/MS was subsequently developed for the simultaneous determination of its metabolites in human plasma. Target analytes consisted of M-5, M-7 and M-8, which were prominently detected by the screening procedure, and M-9, which has pharmacological activity as an H2-receptor antagonist. Metabolites and their deuterated internal standards were extracted from human plasma using an Oasis HLB extraction cartridge, and chromatographed on a Monitor C18M column. No isotope effects on chromatographic retention time were observed for any deuterated compounds, which were ionized using an electrospray ionization (ESI)- interface and detected by MS/MS in the selected reaction-monitoring (SRM) mode simultaneously with the corresponding metabolites. The assay was validated over the concentration range of 0.1 to 25.6 ng ml(-1) and used to determine the plasma levels of metabolites in volunteers following oral administration of a 20-mg dose of pibutidine hydrochloride.
authors.affiliation: Drug Metabolism Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., Omiya, Saitama, Japan. s15379@ccm.taisho.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Jingu
authors.forename: N
authors.initials: N
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D006635:Histamine H2 Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D013058:Mass Spectrometry; D010880:Piperidines / Q000097:blood* / Q000493:pharmacokinetics; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C063924:IT 066