Characterization of growth hormone secretagogue small molecule ibutamoren (MK-0677) and its possible metabolites in thoroughbred horses for doping control.
This study investigated the metabolic profile of ibutamoren (MK-0677) — an orally active, non-peptide growth hormone secretagogue — in thoroughbred horses, with the goal of supporting anti-doping detection efforts. Researchers administered ibutamoren orally to horses and collected biological samples, which were analyzed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to identify and characterize the parent compound and its metabolites. The study identified 22 metabolites in total: 17 Phase I metabolites (including mono- and di-hydroxylated forms, dissociated side chain products such as a benzyl group and 2-amino-2-methylpropanamide, and hydrogenated metabolites) and 5 Phase II metabolites (glucuronic acid conjugates; no sulfate conjugates were detected). The study reported that major metabolites were detectable up to 96 hours post-administration, while the parent compound ibutamoren itself persisted for up to 72 hours. The authors conclude that these findings provide a useful metabolic reference framework to help detect illicit use of ibutamoren in competitive equine sports. Key limitations include the use of an animal model (horses only), meaning findings may not directly translate to human metabolism or human anti-doping contexts.
Why this grade: The study was conducted exclusively in thoroughbred horses with no human subjects, providing no direct human pharmacokinetic or efficacy data.
Rationale It is important to remember that performance-enhancing agents such as non-peptide growth hormone secretagogues present a significant risk of abuse. Ibutamoren (MK-0677) is a potent, long-acting, selective non-peptide growth hormone secretagogue that can be taken orally. Methods This study examines ibutamoren and its metabolites in thoroughbred horses after oral administration. Liquid chromatography/high-resolution mass spectrometry was used to determine the probable structures of the detected metabolites. Results In this study, 22 metabolites of ibutamoren were identified (17 phase I and 5 phase II). Oxidation of ibutamoren leads to hydroxylated metabolites (mono and di). The study also detected dissociated side chains (benzyl group and 2-amino-2-methylpropanamide) and hydrogenated metabolites. The glucuronic acid conjugated analogs of ibutamoren were detected during phase II of the study, but no sulfonic acid conjugated analogs were observed. The major metabolites can be detected up to 96 hours after a single dose, and ibutamoren can persist for up to 72 hours. Conclusions These findings will aid in the detection of ibutamoren and the detection of its illegal use in competitive sports.
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