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In vitro phase I metabolism of selective estrogen receptor modulators in horse using ultra‐high performance liquid chromatography‐high resolution mass spectrometry
Author(s) -
Kwok Karen Y.,
Chan George H. M.,
Kwok Wai Him,
Wong Jenny K. Y.,
Wan Terence S. M.
Publication year - 2017
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2158
Subject(s) - toremifene , tamoxifen , selective estrogen receptor modulator , chemistry , pharmacology , medicine , breast cancer , cancer
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.