In‐depth metabolic study of nonsteroidal selective androgen receptor modulator GSK2881078 in thoroughbred horses and horse liver microsomes for doping control

Abstract

Nonsteroidal selective androgen receptor modulators (SARMs) are a novel class of compounds that have not yet been clinically approved; however, they appear to have a better anabolic/androgenic ratio than steroids and cause slighter side effects. Sports drug testing laboratories are required to maintain continuously updated doping control analytical methods in light of the widespread misuse of SARMs in elite and amateur sports. This paper describes the metabolic conversion of SARM GSK2881078 in thoroughbred horses following oral administration and in vitro with equine liver microsomes. A liquid chromatography-high-resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites. A total of five (M1-M5) in vivo metabolites and six (M1-M6) in vitro metabolites were detected under experimental conditions. Phase I metabolites mainly result from hydroxylation. Methoxylated and side-chain dissociated metabolites were also detected. Neither sulfonic acid nor glucuronic acid conjugated metabolites were observed in this study. Data reported here could aid in the detection of nonsteroidal SARM GSK2881078 and reveal its illicit use in competitive sports.

Electrospray ionization mass spectrometry adduct formation by mobile phase additives: A case study using nitrile functional groups containing selective androgen receptor modulators

“…Our previous studies on SARMs showed multiple adducts in both positive and negative ionization modes. [30][31][32][33] It is possible that the formation of multiple adducts will impact the sensitivity of the analysis and mislead the limit of detection (LOD). Finding the exact cause of adduct formation is necessary to decide which method is appropriate for analysis.…”

“…The aim of this study was to develop a screening method for nitrile functional groups containing SARMs and to investigate the impact of the formation of adducts. The formation of adducts was investigated in 10 SARMs (Figure 1), namely AC-262536, 34,35 ACP-105, 31,36 RAD140,37 LY2452473 (TT-701), 32,38 PF-06260414, 39 GLPG0492 (DT-200), 30,40 LGD-4033 (Ligandrol or VK5211), 41 GSK2881078, 33,42 Ostarine (Enobosarm or MK-2866), 43 and Bicalutamide (ICI-176334 or ZD-176334). 44 This set of molecules was thoroughly examined in both positive and negative ionization modes, allowing for the identification of the most suitable adduct species for each SARM.…”