Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high-resolution mass spectrometry.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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
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 2 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.
