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Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high-resolution mass spectrometry.
Abstract: Selective androgen receptor modulators (SARMs) are prohibited in sports due to their performance enhancing ability. It is important to investigate the metabolism to determine appropriate targets for doping control. This is the first study where the equine metabolites of SARMs S1, S4 (Andarine) and S22 (Ostarine) have been studied in plasma. Methods: Each SARM was administered to three horses as an intravenous bolus dose and plasma samples were collected. The samples were pretreated with protein precipitation using cold acetonitrile before separation by liquid chromatography. The mass spectrometric analysis was performed using negative electrospray, quadrupole time-of-flight mass spectrometry operated in MS(E) mode and triple-quadrupole mass spectrometry operated in selected reaction monitoring mode. For the quantification of SARM S1, a deuterated analogue was used as internal standard. Results: The numbers of observed metabolites were eight, nine and four for the SARMs S1, S4 and S22, respectively. The major metabolite was formed by the same metabolic reactions for all three SARMs, namely amide hydrolysis, hydroxylation and sulfonation. The values of the determined maximum plasma concentrations were in the range of 97-170 ng/mL for SARM S1, 95-115 ng/mL for SARM S4 and 92-147 ng/mL for SARM S22 and the compounds could be detected for 96 h, 12 h and 18 h, respectively. Conclusions: The maximum plasma concentration of SARMs S1, S4 and S22 was measured in the first sample (5 min) after administration and they were eliminated fast from plasma. The proposed targets to be used in equine doping control are the parent compounds for all three SARMs, but with the metabolite yielding the highest response as a complementary target. Copyright © 2016 John Wiley & Sons, Ltd.
Copyright © 2016 John Wiley & Sons, Ltd.
Publication Date: 2016-03-13 PubMed ID: 26969924DOI: 10.1002/rcm.7512Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
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.
The research article focuses on examining the metabolites of Selective Androgen Receptor Modulators (SARMs) S1, S4, and S22 in horse (equine) plasma. These SARMs are often misused in sports since they can enhance athletic performance, thus methods were developed to detect their presence and quantity in plasma for doping control purposes.
Methodology
In the study, each SARM was administered as an intravenous bolus dose (a fast and concentrated dose of a drug) to three horses. The extracted plasma samples were then pretreated with a protein precipitation method using cold acetonitrile to separate the required compounds. Afterwards, liquid chromatography was employed for the separation process. The gathered samples underwent mass spectrometric analysis by means of:
- Negative electrospray
- Quadrupole time-of-flight mass spectrometry operated in MS(E) mode
- Triple-quadrupole mass spectrometry operated in selected reaction monitoring mode
For quantifying SARM S1, a deuterated analogue (a compound with similar structure) was used as the internal standard.
Results
The study yielded varying numbers of observed metabolites – eight for SARM S1, nine for SARM S4, and four for SARM S22. In all three SARMs, the chief metabolite was formed through similar metabolic reactions – amide hydrolysis, hydroxylation, and sulfonation.
The maximum plasma concentrations were:
- SARM S1: 97-170 ng/mL
- SARM S4: 95-115 ng/mL
- SARM S22: 92-147 ng/mL
The detection of these compounds varied, with SARM S1 detectable for 96 hours, SARM S4 for 12 hours, and SARM S22 for 18 hours.
Conclusion
Based on the results, SARMs S1, S4, and S22 were quickly eliminated from plasma, with their highest concentration noted 5 minutes post-administration. The researchers suggest that the parent compounds of all three SARMs can be used as targets in equine doping control, supplemented by the most responsive metabolite for complete detection.
Cite This Article
APA
Hansson A, Knych H, Stanley S, Thevis M, Bondesson U, Hedeland M.
(2016).
Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high-resolution mass spectrometry.
Rapid Commun Mass Spectrom, 30(7), 833-842.
https://doi.org/10.1002/rcm.7512 Publication
Researcher Affiliations
- Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Box 574, SE-75123, Uppsala, Sweden.
- K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
- Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
- K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
- Institute of Biochemistry and Center for Preventive Doping Research, German Sport University, Cologne, Germany.
- 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.
- 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.
MeSH Terms
- Acetamides / analysis
- Acetamides / chemistry
- Acetamides / metabolism
- Amides / analysis
- Amides / chemistry
- Amides / metabolism
- Aminophenols / analysis
- Aminophenols / chemistry
- Aminophenols / metabolism
- Anabolic Agents / analysis
- Anabolic Agents / chemistry
- Anabolic Agents / metabolism
- Androgens / analysis
- Androgens / chemistry
- Androgens / metabolism
- Anilides
- Animals
- Chromatography, High Pressure Liquid
- Female
- Horses
- Limit of Detection
- Tandem Mass Spectrometry
Citations
This article has been cited 3 times.- Tauchen J, Jurášek M, Huml L, Rimpelová S. Medicinal Use of Testosterone and Related Steroids Revisited. Molecules 2021 Feb 15;26(4).
- van Geenen FAMG, Franssen MCR, Miikkulainen V, Ritala M, Zuilhof H, Kostiainen R, Nielen MWF. TiO(2) Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry. J Am Soc Mass Spectrom 2019 Apr;30(4):639-646.
- Taoussi O, Bambagiotti G, Gameli PS, Daziani G, Tavoletta F, Tini A, Basile G, Lo Faro AF, Carlier J. In Vitro and In Vivo Human Metabolism of Ostarine, a Selective Androgen Receptor Modulator and Doping Agent. Int J Mol Sci 2024 Jul 17;25(14).
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