Detection of the selective androgen receptor modulator S-23 and its metabolites in equine urine and plasma following oral administration.
Abstract: S-23 is an arylpropionamide selective androgen receptor modulator that has been investigated in animal models for use as a male hormonal contraceptive but is not yet available therapeutically. S-23 is available alongside other selective androgen receptor modulators (SARMs) to purchase online via uncontrolled sites, sold as supplement products. It has been detected in several human doping cases, highlighting the importance of identifying the best analytical targets for equine doping control. The purpose of this study was to investigate the detection of S-23 and its phase I metabolites in equine urine and plasma following a multiple dose oral administration to two Thoroughbred racehorses. Liquid chromatography-high resolution mass spectrometry was used for metabolite identification, and liquid chromatography-tandem mass spectrometry was used for full sample analysis and generation of urine and plasma profiles. S-23 and seven phase I metabolites were observed in urine following enzyme hydrolysis and solvolysis. The most abundant analyte detected was the hydroxylated 4-amino-2-(trifluoromethyl)benzonitrile metabolite, which also allowed the longest duration of detection in urine from both horses, for up to 360 h following administration. The data suggest that this metabolite was likely to be highly conjugated with both sulphate and glucuronide moieties. In plasma, S-23 and two phase I metabolites were observed. S-23 was the most abundant analyte detected for both horses, allowing detection for up to 143 h post-administration. To the best of the authors' knowledge, this is the first report of S-23 and metabolites in equine urine and plasma samples.
© 2024 John Wiley & Sons, Ltd.
Publication Date: 2024-07-09 PubMed ID: 38982651DOI: 10.1002/dta.3758Google Scholar: Lookup
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Summary
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This research aimed to identify the use of the selective androgen receptor modulator S-23 and its metabolites in horse racing doping, using two Thoroughbred racehorses for testing. The most abundant detected metabolite allowed for detection for up to 360 hours after administration in urine and 143 hours in plasma.
Detection Of S-23 And Its Metabolites
- The research was fonded on the premise that S-23, an arylpropionamide selective androgen receptor modulator, has been available online for purchase despite not being approved for therapeutic purposes. Its detection in human doping cases prompted the need for a study aimed at identifying the substance in equine doping.
- A multiple dose of S-23 was administered orally to two Thoroughbred racehorses, and the detection of the substance and its phase I metabolites was then carried out in equine urine and plasma.
- Liquid chromatography-high resolution mass spectrometry was used to identify the metabolites, and liquid chromatography-tandem mass spectrometry was applied for full sample analysis and the generation of urine and plasma profiles.
Findings
- The study found S-23 and seven phase I metabolites in horse urine following enzyme hydrolysis and solvolysis. It was clear that the 4-amino-2-(trifluoromethyl)benzonitrile metabolite was the most abundant, allowing for the longest duration of detection in urine, for up to 360 hours after administration.
- Based on the data, it appeared that this metabolite was likely highly conjugated with both sulphate and glucuronide moieties.
- In the horse’s plasma, S-23 and two phase I metabolites were observed.
- S-23 was also the most abundant metabolite detected in the plasma, which could be detected for up to 143 hours post-administration.
- This research is the first report of S-23 and its metabolites in equine urine and plasma samples.
Cite This Article
APA
Cutler C, Viljanto M, Hincks P, Habershon-Butcher J, Scarth J, van Eenoo P.
(2024).
Detection of the selective androgen receptor modulator S-23 and its metabolites in equine urine and plasma following oral administration.
Drug Test Anal.
https://doi.org/10.1002/dta.3758 Publication
Researcher Affiliations
- LGC Ltd, Fordham, Cambridgeshire, UK.
- Doping Control Laboratory (DoCoLab), Ghent University, Ghent, Belgium.
- LGC Ltd, Fordham, Cambridgeshire, UK.
- LGC Ltd, Fordham, Cambridgeshire, UK.
- British Horseracing Authority, London, UK.
- LGC Ltd, Fordham, Cambridgeshire, UK.
- Doping Control Laboratory (DoCoLab), Ghent University, Ghent, Belgium.
Grant Funding
- British Horseracing Authority
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