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Drug testing and analysis2020; 13(2); 369-385; doi: 10.1002/dta.2932

Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration.

Abstract: AC-262536 is one of a number of selective androgen receptor modulators that are being developed by the pharmaceutical industry for treatment of a range of clinical conditions including androgen replacement therapy. Though not available therapeutically, selective androgen receptor modulators are widely available to purchase online as (illegal) supplement products. The growth- and bone-promoting effects, along with fewer associated negative side effects compared with anabolic-androgenic steroids, make these compounds a significant threat with regard to doping control in sport. The aim of this study was to investigate the metabolism of AC-262536 in the horse following in vitro incubation and oral administration to two Thoroughbred horses, in order to identify the most appropriate analytical targets for doping control laboratories. Urine, plasma and hair samples were collected and analysed for parent drug and metabolites. Liquid chromatography-high-resolution mass spectrometry was used for in vitro metabolite identification and in urine and plasma samples. Nine phase I metabolites were identified in vitro; four of these were subsequently detected in urine and three in plasma, alongside the parent compound in both matrices. In both urine and plasma samples, the longest detection window was observed for an epimer of the parent compound, which is suggested as the best target for detection of AC-262536 administration. AC-262536 and metabolites were found to be primarily glucuronide conjugates in both urine and plasma. Liquid chromatography-tandem mass spectrometry analysis of post-administration hair samples indicated incorporation of parent AC-262536 into the hair following oral administration. No metabolites were detected in the hair.
© 2020 John Wiley & Sons, Ltd.
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Publication Date: 2020-10-15 PubMed ID: 32959959DOI: 10.1002/dta.2932Google 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.

This research focuses on how horses metabolize a specific selective androgen receptor modulator (AC-262536). The authors conducted a series of tests on Thoroughbred horses to identify optimal detection methods for doping control laboratories, particularly since AC-262536 can be easily bought and misused as a performance-enhancing drug.

Research Objective

  • The main goal of this research was to investigate how the selective androgen receptor modulator, AC-262536, is metabolized by horses. This included both in vitro tests and administering the substance orally to two Thoroughbred horses.
  • Another aim was to find the best analytical targets for doping control laboratories to detect misuse of AC-262536 in sports. It’s especially important because AC-262536, designed as a therapeutic aid for humans, is easily available for illegal purchase online as a supplement.

Methodology

  • The researchers collected urine, plasma, and hair samples from the horses, before and after administering AC-262536 orally.
  • The process of in vitro metabolite identification was carried out using liquid chromatography-high-resolution mass spectrometry.
  • Characterization of the metabolites of AC-262536 was undertaken alongside the detection of the parent compound in urine and plasma.

Findings

  • Nine phase I metabolites were identified during in vitro testing. Out of these, four were detected in urine and three in plasma samples, along with the parent compound, post-administration.
  • An epimer of the parent compound provided the longest detection window both in urine and plasma samples. Therefore, it is suggested as the best target to detect AC-262536 administration.
  • AC-262536 and its metabolites were primarily discovered as glucuronide conjugates in both urine and plasma.
  • Liquid chromatography-tandem mass spectrometry analysis of post-administration hair samples showed incorporation of the parent AC-262536 into the horse’s hair after the drug’s oral administration. Note that no metabolites were detected in the hair samples.

Implications

  • This research provides vital data for doping control laboratories on detecting misuse of AC-262536 in equine sports.
  • Understanding how horses metabolize the drug could aid in ensuring sports integrity and animal welfare.
  • The study’s findings also contribute to the broader knowledge on how selective androgen receptor modulators are metabolized and detected in different biological mediums.

Cite This Article

APA
Cutler C, Viljanto M, Taylor P, Habershon-Butcher J, Muir T, Biddle S, Van Eenoo P. (2020). Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration. Drug Test Anal, 13(2), 369-385. https://doi.org/10.1002/dta.2932

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 13
Issue: 2
Pages: 369-385

Researcher Affiliations

Cutler, Charlotte
  • Sports and Specialised Analytical Services, LGC Ltd, Cambridgeshire, UK.
Viljanto, Marjaana
  • Sports and Specialised Analytical Services, LGC Ltd, Cambridgeshire, UK.
Taylor, Polly
  • Sports and Specialised Analytical Services, LGC Ltd, Cambridgeshire, UK.
Habershon-Butcher, Jocelyn
  • British Horseracing Authority, London, UK.
Muir, Tessa
  • British Horseracing Authority, London, UK.
  • Racing Victoria Ltd, Flemington, Victoria, Australia.
Biddle, Simon
  • Sports and Specialised Analytical Services, LGC Ltd, Cambridgeshire, UK.
Van Eenoo, Peter
  • Laboratory of Doping Control, University of Ghent, Ghent, Belgium.

MeSH Terms

  • Administration, Oral
  • Animals
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / blood
  • Azabicyclo Compounds / metabolism
  • Azabicyclo Compounds / urine
  • Chromatography, Liquid
  • Hair / chemistry
  • Horses / blood
  • Horses / metabolism
  • Horses / urine
  • Naphthalenes / administration & dosage
  • Naphthalenes / blood
  • Naphthalenes / metabolism
  • Naphthalenes / urine
  • Performance-Enhancing Substances / administration & dosage
  • Performance-Enhancing Substances / blood
  • Performance-Enhancing Substances / metabolism
  • Performance-Enhancing Substances / urine
  • Receptors, Androgen / metabolism
  • Substance Abuse Detection
  • Tandem Mass Spectrometry

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