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Home / Equine Research Bank / Drug Test Anal / Investigation of in vitro generated metabolites of GLPG0492 ...
Drug testing and analysis2023; 15(6); 605-628; doi: 10.1002/dta.3453

Investigation of in vitro generated metabolites of GLPG0492 using equine liver microsomes for doping control.

Abstract: An effective alternative to testosterone therapy is selective androgen receptor modulators, a class of compounds that has a tissue-specific effect on muscle and bone. These drugs, which enhance performance, pose a severe abuse risk in competitive sports. GLPG0492 is one of the selective androgen receptor modulators discovered in recent decades. This compound has a unique tissue-specific action for muscle and bone against steroid receptors and acts as a partial agonist for androgen receptors. This study examined GLPG0492 and its metabolites in vitro using equine liver microsomes. Liquid chromatography-high-resolution mass spectrometry was utilized to determine the probable structures of detected metabolites. This study identified 39 metabolites of GLPG0492 (21 phase I and 18 phase II). The hydroxylation of GLPG0492 results in monohydroxylated and dihydroxylated metabolites. Additionally, the study detected dissociated side chains (3-methyl and 4-(hydroxymethyl)) and corresponding hydroxylated metabolites. A series of glucuronic acid- and sulfonic acid-conjugated analogs of GLPG0492 were detected during phase II of the study. The findings might help in the detection of GLPG0492 and the elucidation of its illegal use in equestrian sports.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-02-19 PubMed ID: 36762383DOI: 10.1002/dta.3453Google Scholar: Lookup
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Summary

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The research article discusses a study on GLPG0492, a selective androgen receptor modulator, and examines its metabolites using equine liver microsomes, with the aim of aiding detection of this substance in doping control for equestrian sports.

Study Context and Aim

  • The study revolves around selective androgen receptor modulators (SARMs), particularly GLPG0492, which belong to a class of compounds that impact muscle and bone tissue specifically. Owing to their performance-enhancing effects, these drugs pose a potential abuse risk in competitive sports. The focus here is on the in vitro examination of GLPG0492 and its metabolites using equine liver microsomes.

The Process and Tools

  • The researchers employed liquid chromatography-high-resolution mass spectrometry, a powerful tool frequently used in identifying compound structures, to detect the probable structures of GLPG0492’s metabolites.

Study Findings

  • A total of 39 different metabolites of GLPG0492 were identified and they were divided into two categories: 21 fell under phase I metabolites and 18 were categorized as phase II.
  • One finding was the hydroxylation of GLPG0492, which led to the creation of monohydroxylated and dihydroxylated metabolites. This process involves the addition of a hydroxyl group (a molecule made up of one hydrogen atom bonded to one oxygen atom) to the GLPG0492 compound.
  • Another finding was the detached side chains, labelled as 3-methyl and 4-(hydroxymethyl), and their corresponding hydroxylated metabolites were also detected.
  • During the second phase of the study, the researchers found a sequence of GLPG0492 analogs conjugated with glucuronic acid and sulfonic acid.

Implications of the Study

  • This study offers crucial insights into the metabolites of GLPG0492, which could further aid in the detection of this substance in doping control in equestrian sports.
  • By ascertaining the nature of these metabolites, it might be possible to improve the accuracy and reliability of drug tests, thereby eliminating the illegal use of GLPG0492 in competitive sports.

Cite This Article

APA
Karatt TK, Sathiq MA, Laya S, Philip M, Karakka Kal AK, Subhahar MB. (2023). Investigation of in vitro generated metabolites of GLPG0492 using equine liver microsomes for doping control. Drug Test Anal, 15(6), 605-628. https://doi.org/10.1002/dta.3453

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 15
Issue: 6
Pages: 605-628

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), Tamil Nadu, India.
Sathiq, M Anwar
  • Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tamil Nadu, India.
Laya, Saraswathy
  • Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
Philip, Moses
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Karakka Kal, Abdul Khader
  • 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.

MeSH Terms

  • Animals
  • Horses
  • Receptors, Androgen / metabolism
  • Doping in Sports / prevention & control
  • Microsomes, Liver / metabolism
  • Substance Abuse Detection / methods
  • Androgens / metabolism
  • Androgen Antagonists

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