title: Characterization of equine urinary metabolites of selective androgen receptor modulators (SARMs) S1, S4 and S22 for doping control purposes.
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 3 h 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.
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Box 574, SE-75123, Uppsala, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Hansson
authors.affiliation: K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 956161, USA.|Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, 956161, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Knych
authors.affiliation: K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 956161, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Stanley
authors.affiliation: Institute of Biochemistry and Center for Preventive Doping Research, German Sport University, 50933, Cologne, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Thevis
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Box 574, SE-75123, Uppsala, Sweden.|National Veterinary Institute (SVA), Department of Chemistry, Environment and Feed Hygiene, SE-75651, Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Bondesson
authors.affiliation: Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Box 574, SE-75123, Uppsala, Sweden.|National Veterinary Institute (SVA), Department of Chemistry, Environment and Feed Hygiene, SE-75651, Uppsala, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hedeland
mesh_terms: D045930:Anabolic Agents / Q000378:metabolism / Q000652:urine*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D004300:Doping in Sports; D005260:Female; D006736:Horses / Q000378:metabolism / Q000652:urine*; D006900:Hydroxylation; D059625:Liquid-Liquid Extraction / Q000379:methods / Q000662:veterinary; D013058:Mass Spectrometry / Q000379:methods / Q000662:veterinary; D011944:Receptors, Androgen / Q000378:metabolism*; D052616:Solid Phase Extraction / Q000379:methods / Q000662:veterinary; D015813:Substance Abuse Detection / Q000379:methods / Q000662:veterinary*
chemical_list: D045930:Anabolic Agents; D011944:Receptors, Androgen
keywords: SARM; equine; horse; metabolite; selective androgen receptor modulators