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Drug testing and analysis2023; 15(4); 388-407; doi: 10.1002/dta.3425

Equine metabolism of the selective androgen receptor modulator YK-11 in urine and plasma following oral administration.

Abstract: YK-11 is a steroidal selective androgen receptor modulator, a compound class prohibited in both equine racing and human sports because of their potentially performance enhancing properties. YK-11 is easily accessible via internet-based supplement vendors making this compound a possible candidate for doping; however, its phases I and II metabolism has not yet been reported in the horse. The purpose of this study was to investigate the in vivo metabolites of YK-11 in urine and plasma following oral administration with three daily doses of 50 mg to two Thoroughbred horses. In vitro incubations with equine liver microsomes/S9 were also performed for use as metabolite reference materials; however, this resulted in the formation of 79 metabolites with little overlap with the in vivo metabolism. In plasma, parent YK-11 and seven phase I metabolites were detected, with five of them also observed in vitro. They were present nonconjugated in plasma, with one metabolite also indicating some glucuronide conjugation. In urine, 11 phase I metabolites were observed, with four of them also observed in vitro and six of them also detected in plasma. Nine metabolites were excreted non-conjugated in urine, with two of them also indicating some sulfate conjugation. Two minor metabolites were detected solely as sulfate conjugates. The most abundant analytes in urine were a mono-O-demethylated breakdown product and di-O-demethylated YK-11. The most abundant analytes in plasma were two isomers of the breakdown product with an additional hydroxylation reaction, which also provided the longest detection time in both matrices.
© 2022 John Wiley & Sons Ltd.
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Publication Date: 2023-01-04 PubMed ID: 36519889DOI: 10.1002/dta.3425Google 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 study conducted to investigate how the drug YK-11, a forbidden substance in equine racing and human sports, is metabolized in horses after oral administration. The researchers aimed to identify the metabolites of YK-11 in both urine and plasma for the purpose of enhancing detection methods in anti-doping tests.

YK-11 and its Significance

  • YK-11 is a selective androgen receptor modulator that is banned in equine racing and human sports because of its potential performance-enhancing properties.
  • Despite the prohibition, YK-11 is widely available on the internet, posing a risk of misuse in doping.
  • The study aimed at understanding the metabolism of YK-11 in horses to develop better anti-doping tests.

Experimental Procedure

  • The study proceeded by administering 50mg doses of YK-11 to two thoroughbred horses three times a day.
  • In addition to in vivo tests, in vitro tests were performed using horse liver microsomes/S9. This was done to generate reference material for identifying the metabolites.

Observations & Results

  • The in vitro tests resulted in the formation of 79 metabolites, with a limited overlap with the in vivo metabolism.
  • In the horse’s plasma, YK-11 and seven phase I metabolites were detected, with five of them also seen in the in vitro tests.
  • These compounds were present non-conjugated in plasma, and some were found conjugated with glucuronide.
  • In urine, 11 phase I metabolites were observed, four of which were also seen in vitro and six also detected in plasma.
  • Nine metabolites were excreted non-conjugated in urine, with some indication of sulfate conjugation.
  • A breakdown product, mono-O-demethylated YK-11, and di-O-demethylated YK-11 were the most abundant analytes in urine.
  • In plasma, the most abundant analytes were breakdown products which had an additional hydroxylation reaction. These also provided the longest detection time in both matrices.

This research highlights the complexity of YK-11 metabolism in horses, which might warrant the development of more refined anti-doping tests.

Cite This Article

APA
Harding C, Viljanto M, Habershon-Butcher J, Taylor P, Scarth J. (2023). Equine metabolism of the selective androgen receptor modulator YK-11 in urine and plasma following oral administration. Drug Test Anal, 15(4), 388-407. https://doi.org/10.1002/dta.3425

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 15
Issue: 4
Pages: 388-407

Researcher Affiliations

Harding, Caitlin
  • Sport and Specialised Analytical Services, LGC, Fordham, Cambridgeshire, UK.
Viljanto, Marjaana
  • Sport and Specialised Analytical Services, LGC, Fordham, Cambridgeshire, UK.
Habershon-Butcher, Jocelyn
  • British Horseracing Authority, London, UK.
Taylor, Polly
  • Sport and Specialised Analytical Services, LGC, Fordham, Cambridgeshire, UK.
Scarth, James
  • Sport and Specialised Analytical Services, LGC, Fordham, Cambridgeshire, UK.

MeSH Terms

  • Humans
  • Horses
  • Animals
  • Receptors, Androgen / metabolism
  • Androgens / metabolism
  • Doping in Sports
  • Body Fluids / metabolism
  • Androgen Antagonists
  • Administration, Oral

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Citations

This article has been cited 3 times.
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    doi: 10.1021/acsenvironau.5c00096pubmed: 41583864google scholar: lookup
  2. Zheng S, Ge Y, Fang X, Liu M, Sun H, Deng X, Liao L. Characterization and metabolic profiling of oxymetholone and methasterone metabolites studied with human liver S9 model using GC-Orbitrap-HRMS for anti-doping purposes. Anal Bioanal Chem 2025 Oct;417(24):5499-5512.
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