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Drug testing and analysis2023; 15(7); 757-768; doi: 10.1002/dta.3469

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.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-03-27 PubMed ID: 36922727DOI: 10.1002/dta.3469Google 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 how a new class of substances, nonsteroidal selective androgen receptor modulators (SARMs), could possibly become misused in horse racing sports and an analytical method was developed to detect its use.

Introduction to Nonsteroidal Selective Androgen Receptor Modulators

  • Nonsteroidal selective androgen receptor modulators (SARMs) are a new class of substances that are yet to be clinically approved.
  • They appear to have fewer side effects and a superior anabolic/androgenic ratio (muscle-building versus masculine traits) compared to traditional steroids.
  • Despite not being clinically approved, there is potential for misuse of these SARMs in both elite and amateur sports, as they can enhance performance.

Objective of the Study

  • The study set out to understand the metabolic changes that occur in thoroughbred horses when SARM GSK2881078 is administered orally.
  • The research also investigated the reaction of horse liver microsomes (proteins within liver cells) to GSK2881078 in a lab setting.
  • The objective was to provide accurate methods for doping control laboratories to detect the potential misuse of this particular SARM in sports.

Research Methodology

  • A liquid chromatography-high-resolution mass spectrometry technique was used to study the metabolism of GSK2881078.
  • This technique allowed the researchers to suggest potential structures of the metabolites (substances produced during metabolism) they detected in the horse’s body.

Findings of the Study

  • Five in vivo (in the body of a living organism) metabolites (M1-M5) and six in vitro (outside the body of a living organism) metabolites (M1-M6) of GSK2881078 were detected under the conditions of the experiment.
  • The Phase I metabolites (initial metabolites produced as the body tries to make the substance more water-soluble for excretion) were mainly the result of hydroxylation (a chemical process in which a hydroxyl group is introduced into an organic compound).
  • Methoxylated (where a methoxy group is introduced into the organism) and certain side-chain dissociated metabolites were also detected.
  • Sulfonic acid and glucuronic acid conjugated metabolites, usually present during the second phase of drug metabolism, where the drug becomes more water-soluble, were not observed in this study.

Implications of the Study

  • The data and methods presented in this study could help doping control laboratories to detect the illegal use of SARM GSK2881078 in competitive sports featuring horses.
  • The research thereby contributes to ensuring the integrity of sporting competitions and the welfare of sports animals.

Cite This Article

APA
Karatt TK, Sathiq MA, Laya S, Kal AKK, Subhahar MB, Muhammed Ajeebsanu MP, Philip M, Caveney MR, Graiban FM. (2023). In-depth metabolic study of nonsteroidal selective androgen receptor modulator GSK2881078 in thoroughbred horses and horse liver microsomes for doping control. Drug Test Anal, 15(7), 757-768. https://doi.org/10.1002/dta.3469

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 15
Issue: 7
Pages: 757-768

Researcher Affiliations

Karatt, Tajudheen K
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
  • Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tiruchirappalli, Tamil Nadu, India.
Sathiq, M Anwar
  • Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tiruchirappalli, Tamil Nadu, India.
Laya, Saraswathy
  • Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
Kal, Abdul Khader Karakka
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Subhahar, Michael Benedict
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Muhammed Ajeebsanu, M P
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Philip, Moses
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Caveney, Marina Rodriguez
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Graiban, Fatma Mohammed
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.

MeSH Terms

  • Horses
  • Animals
  • Doping in Sports
  • Microsomes, Liver / metabolism
  • Receptors, Androgen / metabolism
  • Androgens / metabolism
  • Substance Abuse Detection / methods
  • Androgen Antagonists / metabolism
  • Anabolic Agents / metabolism

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Citations

This article has been cited 1 times.
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