Investigation of in vitro generated metabolites of GLPG0492 using equine liver microsomes for doping control

• Published in: Drug testing and analysis 2023-06, Vol.15 (6), p.605-628
• Main Authors: Karatt, Tajudheen K., Sathiq, M. Anwar, Laya, Saraswathy, Philip, Moses, Karakka Kal, Abdul Khader, Subhahar, Michael Benedict
• Format: Article
• Language: English
• Subjects: Androgen Antagonists; Androgens; Androgens - metabolism; Animals; doping control; Doping in Sports - prevention & control; GLPG0492; Horses; in vitro; Metabolites; Microsomes, Liver - metabolism; Receptors, Androgen - metabolism; SARMs; selective androgen receptor modulators; Substance Abuse Detection - methods
• ISSN: 1942-7603; 1942-7611
• DOI: 10.1002/dta.3453

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. The aim of this study was to examine GLPG0492 and its metabolites in vitro using equine liver microsomes. To determine the probable structures of detected metabolites, liquid chromatography–high‐resolution mass spectrometry was used. In this study, 39 metabolites of GLPG0492 were identified (21 phase I and 18 phase II); these findings might be helpful in detecting and explaining GLPG0492's illegal use in equestrian sports.