Equine in vivo metabolite profiling of the selective androgen receptor modulator LGD-3303 for doping control.

This research explores the metabolism of the banned performance-enhancing substance, LGD-3303, in horses to identify new detection targets for doping control.

Introduction

• The study revolves around Selective Androgen Receptor Modulator (SARM) LGD-3303, a potent anabolic agent that is banned in equine and human sports.
• The aim was to explore the in vivo metabolism of this substance in horses and denote potential metabolites that could be used as novel targets for equine doping control.

Methodology

• The researchers administered 0.05 mg·kg LGD-3303 to horses orally and collected blood and urine samples up to 96 hours after administration.
• The in vivo samples, comprising plasma, urine, and hydrolyzed urine, were analyzed using ultra-high performance liquid chromatography coupled to a Q Exactive™ Orbitrap™ high-resolution mass spectrometer with a heated electrospray ionization source.

Findings

• Eight metabolites of LGD-3303 were tentatively identified.
• This includes a carboxylated metabolite as well as several hydroxylated metabolites combined with glucuronic acid conjugates.
• A monohydroxylated metabolite is suggested as an analytical target for doping control analysis of plasma and urine after hydrolysis with β-glucuronidase.
• This particular metabolite is proposed due to its high-intensity signal and prolonged detection time when compared to the parent compound, LGD-3303.

Implications

• The research sheds light on the metabolism of LGD-3303 in equine species and uncovers potential new markers for identifying its illegal use in sports.