Rapid characterization of urinary metabolites of pibutidine hydrochloride in humans by liquid chromatography/electrospray ionization tandem mass spectrometry.
The metabolic products of pibutidine hydrochloride, a new H(2)-receptor antagonist, in human urine after oral administration of 40 mg/man were characterized by high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) with electrospray ionization (ESI). Two-stage collision-induced dissociation (CID) experiments, with in-source CID by increasing the octapole offset voltage and collision-cell CID, were performed in order to develop a very rapid screening procedure that enhanced selectivity toward pibutidine-related compounds. It was possible to detect metabolites of pibutidine directly from a crude biological matrix without prior extraction, enabling confirmation of the identity of eight metabolites in urine. In addition, the linear range in ESI for pibutidine-related compounds was studied to determine the urinary excretion of pibutidine and its metabolites in humans.
Drug Metabolism Laboratory, Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama 330-8530, Japan. s15379@ccm.taisho.co.jp
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Kato
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Jingu
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Ogawa
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Higuchi
D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D006635:Histamine H2 Antagonists / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D012015:Reference Standards
D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C063924:IT 066