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Home / Equine Research Bank / Rapid Commun Mass Spectrom / Metabolic study of selective androgen receptor modulator LY2...
Rapid communications in mass spectrometry : RCM2023; 37(9); e9491; doi: 10.1002/rcm.9491

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control.

Abstract: Since 2010, there has been an increasing number of adverse analytical findings related to selective androgen receptor modulators (SARMs) in competitive sports. It emphasizes the importance of comprehensive doping control analytical procedures that are capable of detecting SARM misuse. Methods: In this study, it is described how LY2452473, a SARM, was metabolized in thoroughbred horses after a single-dose oral administration and in vitro with equine liver microsome preparations. An investigation of the metabolism of LY2452473 in horses' urine, plasma, and hair matrices was carried out during the study. The plausible structures of the detected metabolites were postulated using high-performance liquid chromatography-high resolution mass spectrometry. Results: Under the experimental conditions 15 metabolites (12 phase I and three conjugates of phase I) were detected (M1-M15). The major phase I metabolites identified were formed by hydroxylation. Side-chain dissociated and methylated metabolites were also detected. In phase II, the glucuronic acid and sulfonic acid conjugates of hydroxy LY2452473 were detected as the major metabolites. In vitro analysis has confirmed the presence of all metabolites found in vivo except for the methylated analogs M11 and M12. A peak concentration of LY2452473 (0.5 pg/mg) in proximal hair segments was achieved 4 weeks after administration, according to hair analysis. Conclusions: Data obtained will aid in identifying LY2452473 and related substances faster. Furthermore, the results will assist in checking for the illegal use of these substances in competitive sports.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-02-10 PubMed ID: 36758220DOI: 10.1002/rcm.9491Google Scholar: Lookup
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Summary

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The research seeks to study the metabolism of a selective androgen receptor modulator (SARM), LY2452473, in thoroughbred horses. The aim is to better understand doping control measures by identifying metabolites resulting from the misuse of SARMs in competitive sports.

Methods

  • For this study, the metabolism of the SARM LY2452473 was examined in thoroughbred horses after they had been given a single-dose oral administration. This was also carried out in vitro using equine liver microsome preparations.
  • The researchers studied the metabolism of LY2452473 in various biological samples of the horses – urine, plasma and hair. They aimed to hypothesize the probable structures of detected metabolites.
  • The detection and identification of these metabolites was done using high-performance liquid chromatography-high resolution mass spectrometry, an advanced instrumental technique for the analysis and identification of compounds in a sample.

Results

  • The results from the study showed that under the particular conditions of the experiment, 15 metabolites (12 from phase I and three conjugates from phase I) were detected.
  • The significant phase I metabolites identified were created by a process called hydroxylation. Metabolites that had dissociated from the side-chain as well as methylated metabolites were also found.
  • During phase II, metabolites conjugated with glucuronic acid and sulfonic acid were spotted as the main metabolites of the hydroxy LY2452473.
  • Interestingly, the study’s in vitro analysis confirmed the presence of all metabolites found in vivo except for two methylated variants, M11 and M12.
  • A peak concentration of LY2452473 (0.5 pg/mg) was discovered in proximal hair segments 4 weeks after administration according to hair analysis.

Conclusions

  • The data gathered from this study will help in the faster identification of LY2452473 and associated compounds.
  • The research findings will also be beneficial in enhancing measures intended to monitor and curb the illicit use of these substances in competitive sports, particularly in racehorses.

Cite This Article

APA
Karatt TK, Sathiq MA, Laya S, Karakka Kal AK, Subhahar MB, M P MA, Philip M, Graiban FM, Caveney MR. (2023). Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control. Rapid Commun Mass Spectrom, 37(9), e9491. https://doi.org/10.1002/rcm.9491

Publication

Rapid communications in mass spectrometry : RCM
ISSN: 1097-0231
NlmUniqueID: 8802365
Country: England
Language: English
Volume: 37
Issue: 9
Pages: e9491

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.
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.
M P, Muhammed Ajeebsanu
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Philip, Moses
  • 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.
Caveney, Marina Rodriguez
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.

MeSH Terms

  • Horses
  • Animals
  • Doping in Sports
  • Receptors, Androgen / metabolism
  • Androgens
  • Mass Spectrometry / methods
  • Substance Abuse Detection / veterinary
  • Substance Abuse Detection / methods

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Citations

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