In-depth metabolic study of nonsteroidal selective androgen receptor modulator GSK2881078 in thoroughbred horses and horse liver microsomes for doping control

IF 2.6 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Drug Testing and Analysis Pub Date : 2023-03-15 DOI:10.1002/dta.3469

Tajudheen K. Karatt, M. Anwar Sathiq, Saraswathy Laya, Abdul Khader Karakka Kal, Michael Benedict Subhahar, M. P. Muhammed Ajeebsanu, Moses Philip, Marina Rodriguez Caveney, Fatma Mohammed Graiban

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引用次数: 0

Abstract

Nonsteroidal selective androgen receptor modulators (SARMs) are a novel class of compounds that have not yet been clinically approved; however, they appear to have a better anabolic/androgenic ratio than steroids and cause slighter side effects. Sports drug testing laboratories are required to maintain continuously updated doping control analytical methods in light of the widespread misuse of SARMs in elite and amateur sports. This paper describes the metabolic conversion of SARM GSK2881078 in thoroughbred horses following oral administration and in vitro with equine liver microsomes. A liquid chromatography–high-resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites. A total of five (M1–M5) in vivo metabolites and six (M1–M6) in vitro metabolites were detected under experimental conditions. Phase I metabolites mainly result from hydroxylation. Methoxylated and side-chain dissociated metabolites were also detected. Neither sulfonic acid nor glucuronic acid conjugated metabolites were observed in this study. Data reported here could aid in the detection of nonsteroidal SARM GSK2881078 and reveal its illicit use in competitive sports.

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非甾体选择性雄激素受体调节剂GSK2881078在纯种马和马肝微粒体中的代谢研究

非甾体选择性雄激素受体调节剂是一类尚未获得临床批准的新型化合物；然而，它们似乎比类固醇具有更好的合成代谢/雄激素比率，并引起轻微的副作用。鉴于精英和业余体育运动中普遍滥用严重急性呼吸系统综合征药物，体育药物检测实验室必须不断更新兴奋剂控制分析方法。本文描述了口服给药后和在体外用马肝微粒体对SARM GSK2881078在纯种马中的代谢转化。使用液相色谱-高分辨率质谱法来推测检测到的代谢物的合理结构。在实验条件下，共检测到5种（M1–M5）体内代谢物和6种（M1-M6）体外代谢物。I期代谢产物主要由羟基化作用产生。还检测到甲氧基化和侧链解离的代谢物。本研究中未观察到磺酸和葡萄糖醛酸结合的代谢产物。这里报告的数据可能有助于检测非甾体严重急性呼吸系统综合征GSK2881078，并揭示其在竞技体育中的非法使用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

5.90

自引率

24.10%

发文量

191

审稿时长

2.3 months

期刊介绍： As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.