title: In vitro phase I metabolism of selective estrogen receptor modulators in horse using ultra-high performance liquid chromatography-high resolution mass spectrometry.
abstract: Selective estrogen receptor modulators (SERMs) are chemicals that possess the anti-oestrogenic activities that are banned 'in' and 'out' of competition by the World Anti-Doping Agency (WADA) in human sports, and by the International Federation of Horseracing Authorities (IFHA) in horseracing. SERMs can be used as performance-enhancing drugs to boost the level of androgens or to compensate for the adverse effects as a result of extensive use of androgenic anabolic steroids (AASs). SERMs have indeed been abused in human sports; hence, a similar threat can be envisaged in horseracing. Numerous analytical findings attributed to the use of SERMs have been reported by WADA-accredited laboratories, including 42 cases of tamoxifen and 2 cases of toremifene in 2014. This paper describes the identification of the in vitro phase I metabolites of tamoxifen and toremifene using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS), with an aim to identify potential screening targets for doping control in equine sports. A total of 13 and 11 in vitro metabolites have been identified for tamoxifen and toremifene, respectively, after incubation with homogenized horse liver. The more prominent in vitro biotransformation pathways include N-desmethylation, hydroxylation, and carboxylation. In addition, this is the first report of some novel metabolites for both tamoxifen and toremifene with hydroxylation occurring at the N-methyl moiety. To our knowledge, this is the first study of the phase I metabolism of tamoxifen and toremifene in horses using homogenized horse liver. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China.
authors.forename: Karen Y
authors.identifier: http://orcid.org/0000-0002-0839-8987
authors.initials: KY
authors.lastname: Kwok
authors.affiliation: Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China.
authors.forename: George H M
authors.initials: GHM
authors.lastname: Chan
authors.affiliation: Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China.
authors.forename: Wai Him
authors.initials: WH
authors.lastname: Kwok
authors.affiliation: Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China.
authors.forename: Jenny K Y
authors.identifier: http://orcid.org/0000-0001-8245-6770
authors.initials: JKY
authors.lastname: Wong
authors.affiliation: Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China.
authors.forename: Terence S M
authors.initials: TSM
authors.lastname: Wan
mesh_terms: D045930:Anabolic Agents / Q000032:analysis* / Q000737:chemistry; D000728:Androgens / Q000032:analysis* / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006736:Horses; D006801:Humans; D006900:Hydroxylation; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D017312:Toremifene / Q000032:analysis / Q000737:chemistry*
chemical_list: D045930:Anabolic Agents; D000728:Androgens; D020845:Selective Estrogen Receptor Modulators; D017312:Toremifene
keywords: high resolution; horse; in vitro phase I metabolism; mass spectrometry; tamoxifen; toremifene