In vitro phase I metabolism of selective estrogen receptor modulators in horse using ultra-high performance liquid chromatography-high resolution mass spectrometry
Deutscher übersetzter Titel: | In-vitro-Phase-I-Metabolismus selektiver Östrogen-Rezeptor-Modulatoren bei Pferden durch Ultrahochleistungs-Flüssigkeitschromatographie/hochauflösende Massenspektrometrie |
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Autor: | Kwok, Karen Y.; Chan, George Ho-Man; Kwok, Wai Him; Wong, Jenny K.Y.; Wan, Terence See Ming |
Erschienen in: | Drug testing and analysis |
Veröffentlicht: | 9 (2017), 9/10 (Advances in equine anti-doping), S. 1349-1362, Lit. |
Format: | Literatur (SPOLIT) |
Publikationstyp: | Zeitschriftenartikel |
Medienart: | Elektronische Ressource (online) Gedruckte Ressource |
Sprache: | Englisch |
ISSN: | 1942-7603, 1942-7611 |
DOI: | 10.1002/dta.2158 |
Schlagworte: | |
Online Zugang: | |
Erfassungsnummer: | PU201711010161 |
Quelle: | BISp |
Abstract des Autors
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.