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Drug testing and analysis2021; 14(2); 349-370; doi: 10.1002/dta.3189

Identification of equine in vitro metabolites of seven non-steroidal selective androgen receptor modulators for doping control purposes.

Abstract: Selective androgen receptor modulators, SARMs, are a large class of compounds developed to provide therapeutic anabolic effects with minimal androgenic side effects. A wide range of these compounds are available to purchase online and thus provide the potential for abuse in sports. Knowledge of the metabolism of these compounds is essential to aid their detection in doping control samples. In vitro models allow a quick, cost-effective response where administration studies are yet to be carried out. In this study, the equine phase I metabolism of the non-steroidal SARMs GSK2881078, LGD-2226, LGD-3303, PF-06260414, ACP-105, RAD-140 and S-23 was investigated using equine liver microsomes. Liquid chromatography coupled to a QExactive Orbitrap mass spectrometer allowed identification of metabolites with high resolution and mass accuracy. Three metabolites were identified for both GSK2881078 and LGD-2226, four for LGD-3303 and RAD-140, five for PF-06260414, twelve for ACP-105 and ten for S-23. The equine metabolism of GSK-2881078, LGD-2226, LGD-3303 and PF-06260414 is reported for the first time. Although the equine metabolism of ACP-105, RAD-140 and S-23 has previously been reported, the results obtained in this study have been compared with published data.
© 2021 John Wiley & Sons, Ltd.
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Publication Date: 2021-12-10 PubMed ID: 34714606DOI: 10.1002/dta.3189Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the identification of how horses metabolise non-steroidal selective androgen receptor modulators (SARMs), focusing on seven specific ones. These findings are crucial for detecting their misuse in horseracing and other horse sports.

Objective of the Research

  • The main aim of the study was to understand the metabolism of non-steroidal selective androgen receptor modulators (SARMs) in horses. This is particularly important since these substances can be abused in horse sports to improve performance.
  • A secondary goal was to provide foundations for adequate doping controls in sports involving horses. By understanding the metabolic process, the researchers hope to improve detection methods for these drugs in equine doping control samples.

Selective Androgen Receptor Modulators (SARMs)

  • SARMs are a class of drugs designed to provide therapeutic anabolic effects (those involving the building up of tissues), while minimising the androgenic side effects (those related to male hormone activity).
  • A variety of these compounds can be easily purchased online, increasing the potential for misuse in sports like horseracing.

Approach and Methodology

  • The researchers examined the phase I metabolism processes of seven non-steroidal SARMs by using in vitro models, specifically equine liver microsomes. This was a more time- and cost-effective approach compared to immediately conducting administration studies.
  • The SARMs studied were GSK2881078, LGD-2226, LGD-3303, PF-06260414, ACP-105, RAD-140, and S-23.
  • A combination of liquid chromatography and a QExactive Orbitrap mass spectrometer was used to identify the metabolites of these drugs. This setup provided high resolution and accurate measurement of mass.

Findings

  • Three metabolites each were identified for GSK2881078 and LGD-2226, four each for LGD-3303 and RAD-140, five for PF-06260414, twelve for ACP-105, and ten for S-23.
  • This was the first time the metabolism of GSK-2881078, LGD-2226, LGD-3303, and PF-06260414 was reported in horses.
  • Although the equine metabolism of ACP-105, RAD-140, and S-23 had been reported before, the study’s results were compared with the previously collected data.

Cite This Article

APA
Cutler C, Viljanto M, Taylor P, Hincks P, Biddle S, Van Eenoo P. (2021). Identification of equine in vitro metabolites of seven non-steroidal selective androgen receptor modulators for doping control purposes. Drug Test Anal, 14(2), 349-370. https://doi.org/10.1002/dta.3189

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 14
Issue: 2
Pages: 349-370

Researcher Affiliations

Cutler, Charlotte
  • LGC Ltd, Fordham, UK.
  • Doping Control Laboratory, Ghent University (UGent), Ghent, Belgium.
Viljanto, Marjaana
  • LGC Ltd, Fordham, UK.
Taylor, Polly
  • LGC Ltd, Fordham, UK.
Hincks, Pamela
  • LGC Ltd, Fordham, UK.
Biddle, Simon
  • LGC Ltd, Fordham, UK.
Van Eenoo, Peter
  • Doping Control Laboratory, Ghent University (UGent), Ghent, Belgium.

MeSH Terms

  • Anabolic Agents / metabolism
  • Androgens / analysis
  • Animals
  • Chromatography, Liquid / methods
  • Doping in Sports
  • Horses
  • Receptors, Androgen / metabolism
  • Substance Abuse Detection / methods
  • Substance Abuse Detection / veterinary

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