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Drug testing and analysis2020; 13(2); 318-337; doi: 10.1002/dta.2920

Metabolic studies of selective androgen receptor modulators RAD140 and S-23 in horses.

Abstract: This paper describes the studies of the in vitro biotransformation of two selective androgen receptor modulators (SARMs), namely, RAD140 and S-23, and the in vivo metabolism of RAD140 in horses using ultra-high performance liquid chromatography-high resolution mass spectrometry. in vitro metabolic studies of RAD140 and S-23 were performed using homogenised horse liver. The more prominent in vitro biotransformation pathways for RAD140 included hydrolysis, hydroxylation, glucuronidation and sulfation. Metabolic pathways for S-23 were similar to those for other arylpropionamide-based SARMs. The administration study of RAD140 was carried out using three retired thoroughbred geldings. RAD140 and the majority of the identified in vitro metabolites were detected in post-administration urine samples. For controlling the misuse of RAD140 in horses, RAD140 and its metabolite in sulfate form gave the longest detection time in hydrolysed urine and could be detected for up to 6 days post-administration. In plasma, RAD140 itself gave the longest detection time of up to 13 days. Apart from RAD140 glucuronide, the metabolites of RAD140 described herein have never been reported before.
© 2020 John Wiley & Sons, Ltd.
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Publication Date: 2020-09-06 PubMed ID: 32853476DOI: 10.1002/dta.2920Google Scholar: Lookup
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  • Journal Article

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 explores how horses metabolize two specific selective androgen receptor modulators (SARMs), RAD140 and S-23, with an aim to better understand and control their misuse in horse racing.

Methodology

  • In this study, RAD140 and S-23, which are two types of SARMs, underwent in vitro (in a controlled environment like a petri dish) metabolic studies using horse liver homogenates for observation.
  • This study also involved an in vivo (in an organism) metabolic study of RAD140. Three retired thoroughbreds were administered RAD140 and their subsequent urine and blood samples were analyzed.
  • Ultra-high performance liquid chromatography-high resolution mass spectrometry was leveraged for these analyses, which is a powerful technique for monitoring and identifying chemicals in biological samples.

Findings

  • For RAD140, the primary in vitro biotransformation pathways included hydrolysis (breakdown of a compound due to reaction with water), hydroxylation (introduction of a hydroxyl group into a molecule), glucuronidation (combination with glucuronic acid), and sulfation (combination with a sulfate group).
  • The metabolic pathways for S-23 were found to be similar to those observed for other arylpropionamide-based SARMs.
  • Post-administration, RAD140 and most of the identified in vitro metabolites were detected in the urine samples of the horses. Among these, the longest detection time was given by RAD140 and its metabolite in sulfate form, which were detectable upto 6 days post administration.
  • In the plasma sample, RAD140 showed the longest detection time of upto 13 days.
  • The metabolites of RAD140 that were observed in this study had not been previously reported, aside from the glucuronide of RAD140.

Implications

  • The results of this study can be instrumental in controlling the misuse of RAD140 in horse racing, given the identified metabolites and their detection periods.
  • This research contributes to the broader understanding of how horses metabolize SARMs and could influence drug testing policy and practice in the equestrian world.

Cite This Article

APA
So YM, Wong JKY, Choi TLS, Prabhu A, Stewart B, Farrington AF, Robinson P, Wan TSM, Ho ENM. (2020). Metabolic studies of selective androgen receptor modulators RAD140 and S-23 in horses. Drug Test Anal, 13(2), 318-337. https://doi.org/10.1002/dta.2920

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 13
Issue: 2
Pages: 318-337

Researcher Affiliations

So, Yat-Ming
  • Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Wong, Jenny K Y
  • Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Choi, Timmy L S
  • Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Prabhu, Anil
  • Department of Veterinary Regulation, Welfare & Biosecurity Policy, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Stewart, Brian
  • Department of Veterinary Regulation, Welfare & Biosecurity Policy, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Farrington, Adrian F
  • Department of Veterinary Clinical Services, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Robinson, Paul
  • Department of Veterinary Clinical Services, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Wan, Terence S M
  • Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.
Ho, Emmie N M
  • Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T., Hong Kong, China.

MeSH Terms

  • Anilides / metabolism
  • Anilides / urine
  • Animals
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Doping in Sports
  • Horses / metabolism
  • Horses / urine
  • Mass Spectrometry
  • Metabolic Networks and Pathways
  • Nitriles / metabolism
  • Nitriles / urine
  • Oxadiazoles / metabolism
  • Oxadiazoles / urine
  • Receptors, Androgen / metabolism
  • Substance Abuse Detection

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Citations

This article has been cited 2 times.
  1. Wagener F, Naumann N, Göldner V, Görgens C, Guddat S, Karst U, Thevis M. Comparison of in vitro approaches for predicting the metabolism of the selective androgen receptor modulator RAD140.. Anal Bioanal Chem 2023 Sep;415(23):5657-5669.
    doi: 10.1007/s00216-023-04835-zpubmed: 37421437google scholar: lookup
  2. Wagener F, Euler L, Görgens C, Guddat S, Thevis M. Human In Vivo Metabolism and Elimination Behavior of Micro-Dosed Selective Androgen Receptor Modulator RAD140 for Doping Control Purposes.. Metabolites 2022 Jul 20;12(7).
    doi: 10.3390/metabo12070666pubmed: 35888790google scholar: lookup
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