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Detection of the selective androgen receptor modulator S‐23 and its metabolites in equine urine and plasma following oral administration

(2025) DRUG TESTING AND ANALYSIS. 17(5). p.601-611
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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. S-23, an arylpropionamide selective androgen receptor modulator, presents a significant threat to sports doping. An equine oral administration showed that a hydroxylated amide hydrolysis metabolite was the best analytical target in equine urine, detected as sulphate and glucuronide conjugates. Parent S-23 was the best target in plasma. image
Keywords
arylpropionamide, doping control, horse, metabolism, SARMs, SARMS, S22, S1, S4

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MLA
Cutler, Charlotte, et al. “Detection of the Selective Androgen Receptor Modulator S‐23 and Its Metabolites in Equine Urine and Plasma Following Oral Administration.” DRUG TESTING AND ANALYSIS, vol. 17, no. 5, 2025, pp. 601–11, doi:10.1002/dta.3758.
APA
Cutler, C., Viljanto, M., Hincks, P., Habershon‐Butcher, J., Scarth, J., & Van Eenoo, P. (2025). Detection of the selective androgen receptor modulator S‐23 and its metabolites in equine urine and plasma following oral administration. DRUG TESTING AND ANALYSIS, 17(5), 601–611. https://doi.org/10.1002/dta.3758
Chicago author-date
Cutler, Charlotte, Marjaana Viljanto, Pamela Hincks, Jocelyn Habershon‐Butcher, James Scarth, and Peter Van Eenoo. 2025. “Detection of the Selective Androgen Receptor Modulator S‐23 and Its Metabolites in Equine Urine and Plasma Following Oral Administration.” DRUG TESTING AND ANALYSIS 17 (5): 601–11. https://doi.org/10.1002/dta.3758.
Chicago author-date (all authors)
Cutler, Charlotte, Marjaana Viljanto, Pamela Hincks, Jocelyn Habershon‐Butcher, James Scarth, and Peter Van Eenoo. 2025. “Detection of the Selective Androgen Receptor Modulator S‐23 and Its Metabolites in Equine Urine and Plasma Following Oral Administration.” DRUG TESTING AND ANALYSIS 17 (5): 601–611. doi:10.1002/dta.3758.
Vancouver
1.
Cutler C, Viljanto M, Hincks P, Habershon‐Butcher J, Scarth J, Van Eenoo P. Detection of the selective androgen receptor modulator S‐23 and its metabolites in equine urine and plasma following oral administration. DRUG TESTING AND ANALYSIS. 2025;17(5):601–11.
IEEE
[1]
C. Cutler, M. Viljanto, P. Hincks, J. Habershon‐Butcher, J. Scarth, and P. Van Eenoo, “Detection of the selective androgen receptor modulator S‐23 and its metabolites in equine urine and plasma following oral administration,” DRUG TESTING AND ANALYSIS, vol. 17, no. 5, pp. 601–611, 2025.
@article{01J7GJTNY269T0BEKNSH9CAPTF,
  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.

S-23, an arylpropionamide selective androgen receptor modulator, presents a significant threat to sports doping. An equine oral administration showed that a hydroxylated amide hydrolysis metabolite was the best analytical target in equine urine, detected as sulphate and glucuronide conjugates. Parent S-23 was the best target in plasma. image}},
  author       = {{Cutler, Charlotte and Viljanto, Marjaana and Hincks, Pamela and Habershon‐Butcher, Jocelyn and Scarth, James and Van Eenoo, Peter}},
  issn         = {{1942-7603}},
  journal      = {{DRUG TESTING AND ANALYSIS}},
  keywords     = {{arylpropionamide,doping control,horse,metabolism,SARMs,SARMS,S22,S1,S4}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{601--611}},
  title        = {{Detection of the selective androgen receptor modulator S‐23 and its metabolites in equine urine and plasma following oral administration}},
  url          = {{http://doi.org/10.1002/dta.3758}},
  volume       = {{17}},
  year         = {{2025}},
}

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