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Drug testing and analysis2023; 15(7); 757-768; doi: 10.1002/dta.3469

In-depth metabolic study of nonsteroidal selective androgen receptor modulator GSK2881078 in thoroughbred horses and horse liver microsomes for doping control.

Abstract: Nonsteroidal selective androgen receptor modulators (SARMs) are a novel class of compounds that have not yet been clinically approved; however, they appear to have a better anabolic/androgenic ratio than steroids and cause slighter side effects. Sports drug testing laboratories are required to maintain continuously updated doping control analytical methods in light of the widespread misuse of SARMs in elite and amateur sports. This paper describes the metabolic conversion of SARM GSK2881078 in thoroughbred horses following oral administration and in vitro with equine liver microsomes. A liquid chromatography-high-resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites. A total of five (M1-M5) in vivo metabolites and six (M1-M6) in vitro metabolites were detected under experimental conditions. Phase I metabolites mainly result from hydroxylation. Methoxylated and side-chain dissociated metabolites were also detected. Neither sulfonic acid nor glucuronic acid conjugated metabolites were observed in this study. Data reported here could aid in the detection of nonsteroidal SARM GSK2881078 and reveal its illicit use in competitive sports.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-03-27 PubMed ID: 36922727DOI: 10.1002/dta.3469Google Scholar: Lookup
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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 discusses how a new class of substances, nonsteroidal selective androgen receptor modulators (SARMs), could possibly become misused in horse racing sports and an analytical method was developed to detect its use.

Introduction to Nonsteroidal Selective Androgen Receptor Modulators

  • Nonsteroidal selective androgen receptor modulators (SARMs) are a new class of substances that are yet to be clinically approved.
  • They appear to have fewer side effects and a superior anabolic/androgenic ratio (muscle-building versus masculine traits) compared to traditional steroids.
  • Despite not being clinically approved, there is potential for misuse of these SARMs in both elite and amateur sports, as they can enhance performance.

Objective of the Study

  • The study set out to understand the metabolic changes that occur in thoroughbred horses when SARM GSK2881078 is administered orally.
  • The research also investigated the reaction of horse liver microsomes (proteins within liver cells) to GSK2881078 in a lab setting.
  • The objective was to provide accurate methods for doping control laboratories to detect the potential misuse of this particular SARM in sports.

Research Methodology

  • A liquid chromatography-high-resolution mass spectrometry technique was used to study the metabolism of GSK2881078.
  • This technique allowed the researchers to suggest potential structures of the metabolites (substances produced during metabolism) they detected in the horse’s body.

Findings of the Study

  • Five in vivo (in the body of a living organism) metabolites (M1-M5) and six in vitro (outside the body of a living organism) metabolites (M1-M6) of GSK2881078 were detected under the conditions of the experiment.
  • The Phase I metabolites (initial metabolites produced as the body tries to make the substance more water-soluble for excretion) were mainly the result of hydroxylation (a chemical process in which a hydroxyl group is introduced into an organic compound).
  • Methoxylated (where a methoxy group is introduced into the organism) and certain side-chain dissociated metabolites were also detected.
  • Sulfonic acid and glucuronic acid conjugated metabolites, usually present during the second phase of drug metabolism, where the drug becomes more water-soluble, were not observed in this study.

Implications of the Study

  • The data and methods presented in this study could help doping control laboratories to detect the illegal use of SARM GSK2881078 in competitive sports featuring horses.
  • The research thereby contributes to ensuring the integrity of sporting competitions and the welfare of sports animals.

Cite This Article

APA
Karatt TK, Sathiq MA, Laya S, Kal AKK, Subhahar MB, Muhammed Ajeebsanu MP, Philip M, Caveney MR, Graiban FM. (2023). In-depth metabolic study of nonsteroidal selective androgen receptor modulator GSK2881078 in thoroughbred horses and horse liver microsomes for doping control. Drug Test Anal, 15(7), 757-768. https://doi.org/10.1002/dta.3469

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 15
Issue: 7
Pages: 757-768

Researcher Affiliations

Karatt, Tajudheen K
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
  • Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tiruchirappalli, Tamil Nadu, India.
Sathiq, M Anwar
  • Post Graduate and Research Department of Chemistry, Jamal Mohamed College (Affiliated to Bharathidasan University), Tiruchirappalli, Tamil Nadu, India.
Laya, Saraswathy
  • Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates.
Kal, Abdul Khader Karakka
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Subhahar, Michael Benedict
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Muhammed Ajeebsanu, M P
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Philip, Moses
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Caveney, Marina Rodriguez
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Graiban, Fatma Mohammed
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.

MeSH Terms

  • Horses
  • Animals
  • Doping in Sports
  • Microsomes, Liver / metabolism
  • Receptors, Androgen / metabolism
  • Androgens / metabolism
  • Substance Abuse Detection / methods
  • Androgen Antagonists / metabolism
  • Anabolic Agents / metabolism

References

This article includes 39 references
  1. Kohler M, Thomas A, Walpurgis K, Terlouw K, Schanzer W, Thevis M. Detection of His-tagged long-R3-IGF-I in a black market product.. Growth Horm IGF Res 2010;20(5):386-390.
    doi: 10.1016/j.ghir.2010.07.001google scholar: lookup
  2. Kohler M, Thomas A, Geyer H, Petrou M, Schanzer W, Thevis M. Confiscated black market products and nutritional supplements with non-approved ingredients analyzed in the Cologne Doping Control Laboratory 2009.. Drug Test Anal 2010;2(11-12):533-537.
    doi: 10.1002/dta.186google scholar: lookup
  3. Narayanan R, Mohler ML, Bohl CE, Miller DD, Dalton JT. Selective androgen receptor modulators in preclinical and clinical development.. Nucl Recept Signal 2008;6(1):1-26.
    doi: 10.1621/nrs.06010google scholar: lookup
  4. Zhang X, Sui Z. Deciphering the selective androgen receptor modulators paradigm.. Expert Opin Drug Discovery 2013;8(2):191-218.
    doi: 10.1517/17460441.2013.741582google scholar: lookup
  5. Morimoto M, Aikawa K, Hara T, Yamaoka M. Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models.. Oncol Lett 2017;14(6):8066-8071.
    doi: 10.3892/ol.2017.7200google scholar: lookup
  6. Dalton JT, Taylor RP, Mohler ML, Steiner MS. Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer.. Curr Opin Support Palliat Care 2013;7(4):345-351.
    doi: 10.1097/spc.0000000000000015google scholar: lookup
  7. Thevis M, Schaenzer W, in Handbook of Experimental Pharmacology, Thieme D, Hemmersbach P, eds. 2010, Springer, Heidelberg, Germany. p. 99, doi:10.1007/978-3-540-79088-4_5
    doi: 10.1007/978-3-540-79088-4_5google scholar: lookup
  8. Fragkaki AG, Angelis YS, Koupparis M, Tsantili-Kakoulidou A, Kokotos G, Georgakopoulos C. Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities applied modifications in the steroidal structure.. Steroids 2009;74(2):172-197.
    doi: 10.1016/j.steroids.2008.10.016google scholar: lookup
  9. Chen JY, Kim J, Dalton JT. Discovery and therapeutic promise of selective androgen receptor modulators.. Mol Interv 2005;5(3):173-188.
    doi: 10.1124/mi.5.3.7google scholar: lookup
  10. Wu D, Wu ZR, Yang J, Nair VA, Miller DD, Dalton JT. Pharmacokinetics and metabolism of a selective androgen receptor modulator in rats: implication of molecular properties and intensive metabolic profile to investigate ideal pharmacokinetic characteristics of a propanamide in preclinical study.. Drug Metab Dispos 2006;34(3):483-494.
    doi: 10.1124/dmd.105.006643google scholar: lookup
  11. Cadilla R, Turnbull P. Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential.. Curr Top Med Chem 2006;6(3):245-270.
    doi: 10.2174/156802606776173456google scholar: lookup
  12. Bhasin S, Calof OM, Storer TW. Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging.. Nat Clin Pract Endocrinol Metab 2006;2(3):146-159.
    doi: 10.1038/ncpendmet0120google scholar: lookup
  13. World Anti-Doping Agency. The 2022 prohibited list.. Accessed December 29, 2022.
  14. Bhasin S, Jasuja R. Selective androgen receptor modulators as function promoting therapies.. Curr Opin Clin Nutr Metab Care 2009;12(3):232-240.
    doi: 10.1097/mco.0b013e32832a3d79google scholar: lookup
  15. Gao W, Dalton JT. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs).. Drug Discov Today 2007;12(5-6):241-248.
    doi: 10.1016/j.drudis.2007.01.003google scholar: lookup
  16. Neil D, Clark RV, Magee M. GSK2881078, a SARM, produces dose-dependent increases in lean mass in healthy older men and women.. J Clin Endocrinol Metab 2018;103(9):3215-3224.
    doi: 10.1210/jc.2017-02644google scholar: lookup
  17. Clark RV, Walker AC, Andrews S, Turnbull P, Wald JA, Magee MH. Safety, pharmacokinetics, and pharmacological effects of the selective androgen receptor modulator, GSK2881078, in healthy men and postmenopausal women.. Br J Clin Pharmacol 2017;83(10):2179-2194.
    doi: 10.1111/bcp.13316google scholar: lookup
  18. Hershberger LG, Shipley EG, Meyer RK. Myotrophic activity of 19-nortestosterone and other steroids determined by modified levator ani muscle method.. Proc Soc Exp Biol Med 1953;83(1):175-180.
    doi: 10.3181/00379727-83-20301google scholar: lookup
  19. Thevis M, Schänzer W. Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls.. J Pharm Biomed Anal 2014;101:66-83.
    doi: 10.1016/j.jpba.2014.05.020google scholar: lookup
  20. Thevis M, Schänzer W. Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis-potential implications for sports drug testing programs.. Rapid Commun Mass Spectrom 2016;30(5):635-651.
    doi: 10.1002/rcm.7470google scholar: lookup
  21. Thevis M, Thomas A, Kohler M, Beuck S, Schänzer W. Emerging drugs: mechanism of action, mass spectrometry and doping control analysis.. J Mass Spectrom 2009;44(4):442-460.
    doi: 10.1002/jms.1584google scholar: lookup
  22. Thevis M, Schänzer W. Detection of SARMs in doping control analysis.. Mol Cell Endocrinol 2018;464:34-45.
    doi: 10.1016/j.mce.2017.01.040google scholar: lookup
  23. Thevis M, Volmer DA. Mass spectrometric studies on selective androgen receptor modulators (SARMs) using electron ionization and electrospray ionization/collision-induced dissociation.. Eur J Mass Spectrom 2018;24(1):145-156.
    doi: 10.1177/1469066717731228google scholar: lookup
  24. Thevis M, Schanzer W. Mass spectrometry of selective androgen receptor modulators.. J Mass Spectrom 2008;43(7):865-876.
    doi: 10.1002/jms.1438google scholar: lookup
  25. Stacchini C, Botrè F, Comunità F. Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques.. J Pharm Biomed Anal 2021;195:113849.
    doi: 10.1016/j.jpba.2020.113849google scholar: lookup
  26. de Rijke E, Essers ML, Rijk JCW. Selective androgen receptor modulators: in vitro and in vivo metabolism and analysis.. Food Addit Contam Part a 2013;30(9):1517-1526.
    doi: 10.1080/19440049.2013.810346google scholar: lookup
  27. Subhahar MB, Karakka Kal AK, Philip M. Detection and identification of ACP-105 and its metabolites in equine urine using LC/MS/MS after oral administration.. Drug Test Anal 2021;13(2):299-317.
    doi: 10.1002/dta.2918google scholar: lookup
  28. International Federation of Horseracing Authorities (IFHA). Article 6E, International Agreement on Breeding, Racing and Wagering (IABRW). Available at: International Federation of Horseracing Authorities (ifhaonline.org) [22 December 2022].
  29. Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Koshy SA. Characterization of growth hormone secretagogue small molecule ibutamoren (MK-0677) and its possible metabolites in thoroughbred horses for doping control.. Rapid Commun Mass Spectrom 2022;36(18):e9337.
    doi: 10.1002/rcm.9337google scholar: lookup
  30. Subhahar MB, Singh J, Albert PH, Kadry AM. Pharmacokinetics, metabolism, and excretion of celecoxib, a selective cyclooxygenase-2 inhibitor in horses.. J Vet Pharmacol Therap 2019;42(5):518-524.
    doi: 10.1111/jvp.12757google scholar: lookup
  31. Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z. Hydroxy levamisole and its phase II conjugates as potential indicators of levamisole doping in thoroughbred horses.. Rapid Commun Mass Spectrom 2023;37(3):e9430.
    doi: 10.1002/rcm.9430google scholar: lookup
  32. Karakka Kal AK, Karatt TK, Nalakath J. Simultaneous analysis of 44 frequently abused corticosteroid drugs using polysaccharide-based chiral column-HRMS approach.. Anal Sci Adv 2021;2(9-10):427-439.
    doi: 10.1002/ansa.202000166google scholar: lookup
  33. Karatt TK, Sathiq MA, Laya S. Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control.. Rapid Commun Mass Spectrom 2023;37(9):e949.
    doi: 10.1002/rcm.9491google scholar: lookup
  34. Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z. In vitro studies of hypoxia-inducible factor-prolyl hydroxylase inhibitors daprodustat, desidustat, and vadadustat for equine doping control.. Drug Test Anal 2022;14(2):317-348.
    doi: 10.1002/dta.3188google scholar: lookup
  35. Philip M, Karakka Kal AK, Mathew B, Subhahar MB, Karatt TK, Perwad Z. Metabolic study of hypoxia-inducible factor stabilizers BAY 87-2243, MK-8617, and PT-2385 in equine liver microsomes for doping control.. Drug Test Anal 2022;14(10):1703-1723.
    doi: 10.1002/dta.3348google scholar: lookup
  36. Rading A, Anielski P, Thieme D, Keiler AM. Detection of the selective androgen receptor modulator GSK2881078 and metabolites in urine and hair after single oral administration.. Drug Test Anal 2021;13(1):217-222.
    doi: 10.1002/dta.2943google scholar: lookup
  37. Kowalczyk K, Torres-Elguera JC, Jarek A, Konopka A, Kwiatkowska D, Bulska E. In vitro metabolic studies of novel selective androgen receptor modulators and their use for doping control analysis.. Drug Test Anal 2022;14(1):122-136.
    doi: 10.1002/dta.3151google scholar: lookup
  38. Cutler C, Viljanto M, Taylor P, Hincks P, Biddle S, van Eenoo P. Identification of equine in vitro metabolites of seven non-steroidal selective androgen receptor modulators for doping control purposes.. Drug Test Anal 2022;14(2):349-370.
    doi: 10.1002/dta.3189google scholar: lookup
  39. Karatt TK, Sayed R, Nalakath J, Perwad Z, Albert PH, Abdul Khader KK. Separation and identification of the epimeric doping agents-dexamethasone and betamethasone in equine urine and plasma: a reversed phase chiral chromatographic approach.. Steroids 2018;140:77-82.
    doi: 10.1016/j.steroids.2018.10.003google scholar: lookup

Citations

This article has been cited 1 times.
  1. Thomas A, Walpurgis K, Naumann N, Piper T, Thevis M. Bioanalytical methods in doping controls: a review. Bioanalysis 2025 Mar;17(5):359-370.
    doi: 10.1080/17576180.2025.2460951pubmed: 39916648google scholar: lookup
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