AC‐262536 is one of a number of selective androgen receptor modulators that are being developed by the pharmaceutical industry for treatment of a range of clinical conditions including androgen replacement therapy. Though not available therapeutically, selective androgen receptor modulators are widely available to purchase online as (illegal) supplement products. The growth‐ and bone‐promoting effects, along with fewer associated negative side effects compared with anabolic–androgenic steroids, make these compounds a significant threat with regard to doping control in sport. The aim of this study was to investigate the metabolism of AC‐262536 in the horse following in vitro incubation and oral administration to two Thoroughbred horses, in order to identify the most appropriate analytical targets for doping control laboratories. Urine, plasma and hair samples were collected and analysed for parent drug and metabolites. Liquid chromatography–high‐resolution mass spectrometry was used for in vitro metabolite identification and in urine and plasma samples. Nine phase I metabolites were identified in vitro; four of these were subsequently detected in urine and three in plasma, alongside the parent compound in both matrices. In both urine and plasma samples, the longest detection window was observed for an epimer of the parent compound, which is suggested as the best target for detection of AC‐262536 administration. AC‐262536 and metabolites were found to be primarily glucuronide conjugates in both urine and plasma. Liquid chromatography–tandem mass spectrometry analysis of post‐administration hair samples indicated incorporation of parent AC‐262536 into the hair following oral administration. No metabolites were detected in the hair.

中文翻译：

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选择性雄激素受体调节剂 AC-262536 在体外和口服后尿液、血浆和毛发中的马代谢

AC-262536 是制药行业正在开发的多种选择性雄激素受体调节剂之一，用于治疗包括雄激素替代疗法在内的一系列临床疾病。虽然不能在治疗上获得，但选择性雄激素受体调节剂可作为（非法）补充产品广泛在线购买。与合成代谢雄激素类固醇相比，生长和骨骼促进作用以及相关的负面副作用较少，使这些化合物成为运动兴奋剂控制方面的重大威胁。本研究的目的是在体外研究马体内 AC-262536 的代谢。对两匹纯种马进行孵化和口服给药，以便为兴奋剂控制实验室确定最合适的分析目标。收集尿液、血浆和头发样本并分析母体药物和代谢物。液相色谱-高分辨质谱用于体外代谢物鉴定以及尿液和血浆样品。在体外鉴定了九种 I 期代谢物; 随后在尿液中检测到其中四种，在血浆中检测到三种，以及两种基质中的母体化合物。在尿液和血浆样本中，观察到母体化合物差向异构体的最长检测窗口，这被认为是检测 AC-262536 给药的最佳目标。发现 AC-262536 及其代谢物主要是尿液和血浆中的葡萄糖醛酸结合物。给药后头发样品的液相色谱-串联质谱分析表明，口服给药后母体 AC-262536 掺入了头发中。在头发中未检测到代谢物。