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

(2021) DRUG TESTING AND ANALYSIS. 13(2). p.369-385
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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 followingin vitroincubation 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 forin vitrometabolite identification and in urine and plasma samples. Nine phase I metabolites were identifiedin 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.
Keywords
IN-VITRO TECHNOLOGIES, MASS LC-MS, GENERATED METABOLITES, DRUG-METABOLISM, SARMS, IDENTIFICATION, SPECTROMETRY, THROUGHPUT, LGD-4033, ANDARINE, AC-262536, horse, metabolism, SARMs

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Citation

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MLA
Cutler, Charlotte, et al. “Equine Metabolism of the Selective Androgen Receptor Modulator AC-262536 in Vitro and in Urine, Plasma and Hair Following Oral Administration.” DRUG TESTING AND ANALYSIS, vol. 13, no. 2, 2021, pp. 369–85, doi:10.1002/dta.2932.
APA
Cutler, C., Viljanto, M., Taylor, P., Habershon-Butcher, J., Muir, T., Biddle, S., & Van Eenoo, P. (2021). Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration. DRUG TESTING AND ANALYSIS, 13(2), 369–385. https://doi.org/10.1002/dta.2932
Chicago author-date
Cutler, Charlotte, Marjaana Viljanto, Polly Taylor, Jocelyn Habershon-Butcher, Tessa Muir, Simon Biddle, and Peter Van Eenoo. 2021. “Equine Metabolism of the Selective Androgen Receptor Modulator AC-262536 in Vitro and in Urine, Plasma and Hair Following Oral Administration.” DRUG TESTING AND ANALYSIS 13 (2): 369–85. https://doi.org/10.1002/dta.2932.
Chicago author-date (all authors)
Cutler, Charlotte, Marjaana Viljanto, Polly Taylor, Jocelyn Habershon-Butcher, Tessa Muir, Simon Biddle, and Peter Van Eenoo. 2021. “Equine Metabolism of the Selective Androgen Receptor Modulator AC-262536 in Vitro and in Urine, Plasma and Hair Following Oral Administration.” DRUG TESTING AND ANALYSIS 13 (2): 369–385. doi:10.1002/dta.2932.
Vancouver
1.
Cutler C, Viljanto M, Taylor P, Habershon-Butcher J, Muir T, Biddle S, et al. Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration. DRUG TESTING AND ANALYSIS. 2021;13(2):369–85.
IEEE
[1]
C. Cutler et al., “Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration,” DRUG TESTING AND ANALYSIS, vol. 13, no. 2, pp. 369–385, 2021.
@article{8694577,
  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 followingin vitroincubation 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 forin vitrometabolite identification and in urine and plasma samples. Nine phase I metabolites were identifiedin 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.}},
  author       = {{Cutler, Charlotte and Viljanto, Marjaana and Taylor, Polly and Habershon-Butcher, Jocelyn and Muir, Tessa and Biddle, Simon and Van Eenoo, Peter}},
  issn         = {{1942-7603}},
  journal      = {{DRUG TESTING AND ANALYSIS}},
  keywords     = {{IN-VITRO TECHNOLOGIES,MASS LC-MS,GENERATED METABOLITES,DRUG-METABOLISM,SARMS,IDENTIFICATION,SPECTROMETRY,THROUGHPUT,LGD-4033,ANDARINE,AC-262536,horse,metabolism,SARMs}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{369--385}},
  title        = {{Equine metabolism of the selective androgen receptor modulator AC-262536 in vitro and in urine, plasma and hair following oral administration}},
  url          = {{http://doi.org/10.1002/dta.2932}},
  volume       = {{13}},
  year         = {{2021}},
}

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