Detection of nonsteroidal and steroidal selective androgen receptor modulators in equine hair after oral administrations.
- Journal Article
Summary
The research article discusses a study on the detection of potent anabolic agents, specifically RAD140 and YK-11, in the hair of horses that were orally administered with these substances. The intent was to improve controls on their misuse in horse racing and equestrian sports.
Study Overview
This paper presents the results of an experiment where horses were orally given nonsteroidal and steroidal selective androgen receptor modulators (SARMs), specifically RAD140 and YK-11, in order to understand their metabolism better and create more effective doping controls.
- The researchers wanted to identify the analytes with the longest detection time in urine and plasma, and observe the behavior of these substances in hair samples.
Substances under Study
The objective was to better control the misuse of two specific SARMs, RAD140 and YK-11, substances that have previously been reported as misused in human sports.
- RAD140 and YK-11 are potent anabolic agents. Anabolic agents are substances that promote cell growth, and are often used illegally to enhance performance in sports.
- The horses were administered RAD140 at 0.3 mg/kg daily for three days and YK-11 at 0.2 mg/kg daily over the same period.
Key Findings
After the administration of the said drugs, the researchers examined hair samples from the mane of the horses.
- It was found that both RAD140 and YK-11 could be detected in the hair after oral administration.
- The study revealed that RAD140 entered the hair both internally (via the bloodstream) and externally (through sweat or sebum). Sebum is an oily substance secreted by the skin’s sebaceous glands, which helps to keep the skin and hair moisturized.
- Unlike RAD140, the incorporation of YK-11 into hair was primarily external, via sweat or sebum.
Implication of Findings
The findings of this research could assist in better control of doping in equine sports, specifically horse racing. The ability to detect these substances in hair samples offers a new avenue for policing their misuse. However, this would depend on the development of reliable and valid testing methods based on this research.
Cite This Article
Publication
Researcher Affiliations
- Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T, Hong Kong, China.
- Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T, Hong Kong, China.
- Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T, Hong Kong, China.
- Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T, Hong Kong, China.
- Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T, Hong Kong, China.
- Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N. T, Hong Kong, China.
References
- Mohler ML, Bohl CE, Jones A. Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit.. J Med Chem 2009;52(12):3597‐3617.
- Miller CP, Shomali M, Lyttle CR. Design, synthesis, and preclinical characterization of the selective androgen receptor modulator (SARM) RAD140.. Med Chem Lett 2011;2(2):124‐129.
- Cycling athlete suspended for presence of SARM RAD‐140. Available: https://sirc.ca/news/cycling-athlete-suspended-for-presence-of-sarm-rad-140/ (accessed on 25 February 2024).
- Sobolevsky T, Kucherova Y, Ahrens B. Detection of selective androgen receptor modulator YK‐11 in a doping control sample.. Drug Test Anal 2024;16(6):655‐660.
- World Anti‐Doping Agency (WADA). 2024 Prohibited List. Available: https://www.wada-ama.org/sites/default/files/2023-09/2024list_en_final_22_september_2023.pdf (accessed on 25 February 2024).
- International Federation of Horseracing Authorities (IFHA). Article 6 in the International Agreement on Breeding, Racing and Wagering (IABRW). Available: https://www.ifhaonline.org/default.asp?section=IABRW&AREA=2#article6 (accessed on 25 February 2024).
- Fédération Equestre Internationale (FEI). 2024 Equine Prohibited Substances List. Available: https://inside.fei.org/sites/default/files/2024%20Prohibited%20Substances%20List.pdf (accessed on 25 February 2024).
- So YM, Wong JKY, Choi TLS. Metabolic studies of selective androgen receptor modulators RAD140 and S‐23 in horses.. Drug Test Anal 2021;13(2):318‐337.
- Unpublished results: in vivo metabolic study of YK‐11 in horse urine and plasma.
- Harding C, Viljanto M, Habershon‐Butcher J, Taylor P, Scarth J. Equine metabolism of the selective androgen receptor modulator YK‐11 in urine and plasma following oral administration.. Drug Test Anal 2023;15(4):388‐407.
- Pragst F, Balikova MA. State of the art in hair analysis for detection of drug and alcohol abuse.. Clin Chim Acta 2006;370(1–2):17‐49.
- Kintz P. Hair analysis in forensic toxicology: an updated review with a special focus on pitfalls.. Curr Pharm Des 2017;23(36):5480‐5486.
- Usman M, Naseer A, Baig Y, Jamshaid T, Shahwar M, Khurshuid S. Forensic toxicological analysis of hair: a review.. Egypt J Forensic Sci 2019;9(1):17.
- Gray B, Viljanto M, Menzies E, Vanhaecke L. Detection of prohibited substances in equine hair by ultra‐high performance liquid chromatography‐triple quadrupole mass spectrometry ‐ application to doping control samples.. Drug Test Anal 2018;10(7):1050‐1060.
- Ishii H, Shibuya M, Leung GNW. Detection and longitudinal distribution of GW1516 and its metabolites in equine hair for doping control using liquid chromatography/high‐resolution mass spectrometry.. Rapid Commun Mass Spectrom 2021;35(8):e9050.
- Ishii H, Shibuya M, So YM. Long‐term monitoring of IOX4 in horse hair and its longitudinal distribution with segmental analysis using liquid chromatography/electrospray ionization Q Exactive high‐resolution mass spectrometry for the purpose of doping control.. Drug Test Anal 2022;14(7):1244‐1254.
- Viljanto M, Cutler C, Taylor P, Habershon‐Butcher J, Gray B. Detection of the growth hormone secretagogue MK‐0677 in equine hair following oral administration.. Drug Test Anal 2023;15(3):361‐367.
- Choi TLS, Kwok KY, Kwok WH, Tsoi YYK, Wong JKY, Wan TSM. Detection of seventy‐two anabolic and androgenic steroids and/or their esters in horse hair using ultra‐high performance liquid chromatography‐high resolution mass spectrometry in multiplexed targeted MS2 mode and gas chromatography‐tandem mass spectrometry.. J Chromatogr A 2018;1566:51‐63.
- Knych HL, McKemie DS, Yim S, Stanley SD, Arthur RM. Long‐term monitoring of clodronate in equine hair using liquid chromatography‐tandem mass spectrometry.. J Chromatogr B 2023;1226:123789.
- Cutler C, Viljanto M, Hincks P, Habershon‐Butcher J, Muir T, Biddle S. Investigation of the metabolism of the selective androgen receptor modulator LGD‐4033 in equine urine, plasma and hair following oral administration.. Drug Test Anal 2020;12(2):247‐260.
- Cutler C, Viljanto M, Taylor P. Equine metabolism of the selective androgen receptor modulator AC‐262536 in vitro and in urine, plasma and hair following oral administration.. Drug Test Anal 2021;13(2):369‐385.
- Musshoff F, Madea B. Analytical pitfalls in hair testing.. Anal Bioanal Chem 2007;388(7):1475‐1494.
- Gray B, Bailly‐Chouriberry L, Kwok WH, Yamada S, Yamada M, Moeller B. Association of Official Racing Chemists guidelines for drug testing in animal hair for doping control.. Drug Test Anal 2024; Early View.
- McCutcheon LJ, Geor RJ, Hare MJ, Ecker GL, Lindinger MI. Sweating rate and sweat composition during exercise and recovery in ambient heat and humidity.. Equine Vet J 1992;27(S20):153‐157.
- Dunnett M. The diagnostic potential of equine hair: A comparative review of hair analysis for assessing nutritional status, environmental poisoning, and drug use and abuse.. Advances in Equine Nutrition III 2005:85‐106.
- Henderson GL. Mechanisms of drug incorporation into hair.. Forensic Sci Int 1993;63(1–3):19‐29.
- Association of the Official Racing Chemists, Guidelines for the minimum criteria for identification by chromatography and mass spectrometry. https://www.aorc-online.org/documents/aorc-ms-criteria-ilacg7/ (accessed on 03 June 2024).
- Madry MM, Spycher BS, Kupper J. Long‐term monitoring of opioid, sedative and anti‐inflammatory drugs in horse hair using a selective and sensitive LC‐MS/MS procedure.. BMC Vet Res 2016;1(12):84.
- ChemicalBook. Predicted pKa of RAD140, obtained from the CAS DataBase List: 1182367‐47‐0 in ChemicalBook. Available: https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12628346.htm (accessed on 25 February 2024).
- Rygaard K, Linnet K, Johansen SS. A systematic review of metabolite‐to‐drug ratios of pharmaceuticals in hair for forensic investigations.. Metabolites 2021;11(10):686.
- Chan SJ. Study on the external contamination in hair—amphetamines in sweat. Oral Presentation in the SoHT‐GTFI Joint Meeting 2022.