Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tamil Nadu, India.
Drug Test Anal. 2023 Jun;15(6):605-628. doi: 10.1002/dta.3453. Epub 2023 Feb 19.
An effective alternative to testosterone therapy is selective androgen receptor modulators, a class of compounds that has a tissue-specific effect on muscle and bone. These drugs, which enhance performance, pose a severe abuse risk in competitive sports. GLPG0492 is one of the selective androgen receptor modulators discovered in recent decades. This compound has a unique tissue-specific action for muscle and bone against steroid receptors and acts as a partial agonist for androgen receptors. This study examined GLPG0492 and its metabolites in vitro using equine liver microsomes. Liquid chromatography-high-resolution mass spectrometry was utilized to determine the probable structures of detected metabolites. This study identified 39 metabolites of GLPG0492 (21 phase I and 18 phase II). The hydroxylation of GLPG0492 results in monohydroxylated and dihydroxylated metabolites. Additionally, the study detected dissociated side chains (3-methyl and 4-(hydroxymethyl)) and corresponding hydroxylated metabolites. A series of glucuronic acid- and sulfonic acid-conjugated analogs of GLPG0492 were detected during phase II of the study. The findings might help in the detection of GLPG0492 and the elucidation of its illegal use in equestrian sports.
一种有效的睾酮替代疗法是选择性雄激素受体调节剂，这是一类对肌肉和骨骼具有组织特异性作用的化合物。这些药物可以提高运动表现，在竞技体育中存在严重的滥用风险。GLPG0492 是近几十年来发现的选择性雄激素受体调节剂之一。这种化合物对肌肉和骨骼具有独特的组织特异性作用，对甾体受体具有拮抗作用，对雄激素受体具有部分激动作用。本研究使用马肝微粒体在体外研究了 GLPG0492 及其代谢物。采用液相色谱-高分辨质谱法确定了检测到的代谢物的可能结构。本研究鉴定了 GLPG0492 的 39 种代谢物（21 种 I 相代谢物和 18 种 II 相代谢物）。GLPG0492 的羟化导致单羟化和二羟化代谢物的产生。此外，研究还检测到分离的侧链（3-甲基和 4-（羟甲基））和相应的羟化代谢物。在研究的 II 相中还检测到 GLPG0492 的一系列葡萄糖醛酸和磺酸缀合类似物。这些发现可能有助于检测 GLPG0492 并阐明其在马术运动中的非法使用。
