Characterization of equine urinary metabolites of selective androgen receptor modulators (SARMs) S1, S4 and S22 for doping control purposes.

This study explores how certain performance-enhancing drugs known as selective androgen receptor modulators (SARMs) are metabolized in horses, in efforts to improve anti-doping measures in equestrian sports. The researchers found that the ways horses metabolize these substances differ significantly from humans, and suggest focusing on specific key metabolites as targets for doping control tests.

Understanding SARMs and Doping

• Selective androgen receptor modulators (SARMs) belong to a class of substances that have muscle-building (anabolic) properties with fewer masculine (androgenic) side effects, which makes them potential substances for misuse, especially in athletics where physical prowess is crucial.
• The World Anti-Doping Agency (WADA) has prohibited the entire class of SARMs due to several recorded incidents of misuse.
• The substances have a tendency to be extensively metabolized in humans, necessitating the detection of their metabolites – substances created as the body breaks down the drugs – for anti-doping controls.

Study Objective and Methods

• Despite interest in exploring SARMs’ role in doping controls for horse racing, there were no previous studies into how the substances are metabolized in horses.
• The researchers aimed to elucidate this by studying the urinary metabolites of three types of SARMs – S1, S4, and S22 – in horses after they were intravenously injected, and using a specific type of analytical method known as ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QToF-MS).

Findings and Implications

• The research identified various metabolites for S1, S4, and S22 – eight for S1, nine for S4, and seven for S22.
• The parental compounds were only detected at the first sampling time point 3 hours post administration, making them unsuitable as target compounds for doping detection.
• The researchers found that the metabolite showing the highest response had undergone amide hydrolysis, hydroxylation, and sulfonation – chemical reactions related to the breakdown of the substance in the body. Based on this, the team suggested focusing on these specific phase II metabolites for future equine doping control efforts.
• The findings underscore significant differences in how SARMs are metabolized in humans and horses, which has substantial implications for anti-doping testing procedures and regulations in equestrian sports.