Equine metabolism of the selective androgen receptor modulator YK‐11 in urine and plasma following oral administration

Abstract YK‐11 is a steroidal selective androgen receptor modulator, a compound class prohibited in both equine racing and human sports because of their potentially performance enhancing properties. YK‐11 is easily accessible via internet‐based supplement vendors making this compound a possible candidate for doping; however, its phases I and II metabolism has not yet been reported in the horse. The purpose of this study was to investigate the in vivo metabolites of YK‐11 in urine and plasma following oral administration with three daily doses of 50 mg to two Thoroughbred horses. In vitro incubations with equine liver microsomes/S9 were also performed for use as metabolite reference materials; however, this resulted in the formation of 79 metabolites with little overlap with the in vivo metabolism. In plasma, parent YK‐11 and seven phase I metabolites were detected, with five of them also observed in vitro. They were present nonconjugated in plasma, with one metabolite also indicating some glucuronide conjugation. In urine, 11 phase I metabolites were observed, with four of them also observed in vitro and six of them also detected in plasma. Nine metabolites were excreted non‐conjugated in urine, with two of them also indicating some sulfate conjugation. Two minor metabolites were detected solely as sulfate conjugates. The most abundant analytes in urine were a mono‐O‐demethylated breakdown product and di‐O‐demethylated YK‐11. The most abundant analytes in plasma were two isomers of the breakdown product with an additional hydroxylation reaction, which also provided the longest detection time in both matrices.