title: Analysis of tolvaptan and its metabolites in sports drug testing by high-performance liquid chromatography coupled to tandem mass spectrometry.
abstract: Tolvaptan is prohibited by the World Anti-doping Agency (WADA) under class S5 - Diuretics and masking agents. Less than 1% of the administrated dose is excreted by humans in urine. Knowledge concerning the metabolism in humans, and especially the excretion of metabolites in human urine, is limited. An analysis method based on the dilute-and-shoot approach using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for detection was developed and validated. Ion transitions, which are part of this method, can easily be included in already existing screening methods used in routine doping analysis for the detection of diuretics. After administration of a single dose of tolvaptan to one male subject, low concentrations of the drug itself could be detected in urine samples over a time period of 24 h. In addition, hydroxyl metabolites of tolvaptan and one carboxyl metabolite with a cleaved benzazepine ring system were identified. These metabolites showed detection times of up to 150 h. An inclusion of these metabolites in the methods used in doping control analysis seems therefore to be of value. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Oslo University Hospital, Norwegian Doping Control Laboratory, Oslo, Norway. Sebastian.Rzeppa@dopinganalyse.no.
authors.forename: S
authors.initials: S
authors.lastname: Rzeppa
authors.affiliation: Oslo University Hospital, Norwegian Doping Control Laboratory, Oslo, Norway.|University of Münster, Institute of Food Chemistry, Münster, Germany.
authors.forename: L N
authors.initials: LN
authors.lastname: Viet
mesh_terms: D001552:Benzazepines / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D004232:Diuretics / Q000737:chemistry* / Q000378:metabolism; D004300:Doping in Sports; D006801:Humans; D057230:Limit of Detection; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000077602:Tolvaptan
chemical_list: D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan
keywords: doping analysis; liquid chromatography-mass spectrometry; metabolism; tolvaptan