title: Mass spectrometric identification and characterization of new clomiphene metabolites in human urine by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry.
abstract: Clomiphene, a selective estrogen receptor modulator, is prohibited by World Anti Doping Agency (WADA) out-of-competition and in-competition. As it is extensively metabolized, further investigation of clomiphene metabolic profile will be essential to routine anti-doping analysis. The metabolic pathway and the different metabolites of clomiphene in human urine collected from three healthy volunteers during 1 week were studied by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOFMS) based on accurate mass measurement. Seven unreported metabolites were identified and characterized, and all of the newly found urinary metabolites belonged to a new metabolic pathway (hydrogenation). An approach for the metabolism study of clomiphene and its analogs by LC-QTOFMS was presented. Two metabolites, 3,4-dihydroxy-dihydro-clomiphene (m/z 440.1991) and 3,4-dihydroxy-dihydro-deethyl-clomiphne (m/z 412.1674), are the potential biomarkers for monitoring oral administration of clomiphene in doping control.
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, ChaoYang District, Beijing 100029, China. lujianghai@chinada.cn
authors.forename: Jianghai
authors.initials: J
authors.lastname: Lu
authors.forename: Genye
authors.initials: G
authors.lastname: He
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Youxuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Bo
authors.forename: Gangfeng
authors.initials: G
authors.lastname: Ouyang
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D002996:Clomiphene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine*; D004300:Doping in Sports; D006801:Humans; D008297:Male; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002996:Clomiphene