Characterization of equine urinary metabolites of selective androgen receptor modulators (SARMs) S1, S4 and S22 for doping control purposes

Annelie Hansson, Heather K Knych, Scott D Stanley, Mario Thevis, Ulf Bondesson, Mikael Hedeland

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Selective androgen receptor modulators, SARMs, constitute a class of compounds with anabolic properties but with few androgenic side-effects. This makes them possible substances of abuse and the World Anti-Doping Agency (WADA) has banned the entire class of substances. There have been several cases of illicit use of aryl propionamide SARMs in human sports and in 2013, 13 cases were reported. These substances have been found to be extensively metabolized in humans, making detection of metabolites necessary for doping control. SARMs are also of great interest to equine doping control, but the in vivo metabolite pattern and thus possible analytical targets have not been previously studied in this species. In this study, the urinary metabolites of the SARMs S1, S4, and S22 in horses were studied after intravenous injection, using ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QToF-MS). Eight different metabolites were found for SARM S1, nine for SARM S4, and seven for SARM S22. The equine urinary metabolite profiles differed significantly from those of humans. The parent compounds were only detected for SARMs S4 and S22 and only at the first sampling time point at 3h post administration, making them unsuitable as target compounds. For all three SARMs tested, the metabolite yielding the highest response had undergone amide hydrolysis, hydroxylation and sulfonation. The resulting phase II metabolites (4-nitro-3-trifluoro-methyl-phenylamine sulfate for SARMs S1 and S4 and 4-cyano-3-trifluoro-methyl-phenylamine sulfate for SARM S22) are proposed as analytical targets for use in equine doping control.

Original languageEnglish (US)
Pages (from-to)673-683
Number of pages11
JournalDrug Testing and Analysis
Volume7
Issue number8
DOIs
StatePublished - Aug 1 2015

Fingerprint

androgen
Androgen Receptors
Metabolites
Modulators
Horses
metabolite
Doping (additives)
Aniline Compounds
Sulfates
equine
sulfate
Sulfonation
Hydroxylation
High performance liquid chromatography
horse
Sports
sport
Amides
Intravenous Injections
Substance-Related Disorders

Keywords

  • Equine
  • Horse
  • Metabolite
  • SARM
  • Selective androgen receptor modulators

ASJC Scopus subject areas

  • Analytical Chemistry
  • Environmental Chemistry
  • Pharmaceutical Science
  • Spectroscopy

Cite this

Characterization of equine urinary metabolites of selective androgen receptor modulators (SARMs) S1, S4 and S22 for doping control purposes. / Hansson, Annelie; Knych, Heather K; Stanley, Scott D; Thevis, Mario; Bondesson, Ulf; Hedeland, Mikael.

In: Drug Testing and Analysis, Vol. 7, No. 8, 01.08.2015, p. 673-683.

Research output: Contribution to journalArticle

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