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Drug testing and analysis2020; 12(2); 247-260; doi: 10.1002/dta.2719

Investigation of the metabolism of the selective androgen receptor modulator LGD-4033 in equine urine, plasma and hair following oral administration.

Abstract: LGD-4033 is one of a number of selective androgen receptor modulators (SARMs) that are being developed by the pharmaceutical industry to provide the therapeutic benefits of anabolic androgenic steroids, without the less desirable side effects. Though not available therapeutically, SARMs are available for purchase online as supplement products. The potential for performance enhancing effects associated with these products makes them a significant concern with regards to doping control in sports. The purpose of this study was to investigate the metabolism of LGD-4033 in the horse following oral administration, in order to identify the most appropriate analytical targets for doping control laboratories. LGD-4033 was orally administered to two Thoroughbred horses and urine, plasma and hair samples were collected and analysed for parent drug and metabolites. LC-HRMS was used for metabolite identification in urine and plasma. Eight metabolites were detected in urine, five of which were excreted only as phase II conjugates, with the longest detection time being observed for di- and tri-hydroxylated metabolites. The parent compound could only be detected in urine in the conjugated fraction. Seven metabolites were detected in plasma along with the parent compound where mono-hydroxylated metabolites provided the longest duration of detection. Preliminary investigations with hair samples using LC-MS/MS analysis indicated the presence of trace amounts of the parent compound and one of the mono-hydroxylated metabolites. In vitro incubation of LGD-4033 with equine liver microsomes was also performed for comparison, yielding 11 phase I metabolites. All of the metabolites observed in vivo were also observed in vitro.
© 2019 John Wiley & Sons, Ltd.
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Publication Date: 2020-01-05 PubMed ID: 31655494DOI: 10.1002/dta.2719Google 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.

This study investigates the metabolism of the drug LGD-4033 in horses to understand how the drug is processed in the body, with the intent of better informing doping control measures. It found that certain metabolites could be detected in urine, blood and hair samples from the horses for extended periods of time after administration.

Introduction and Aim

The researchers are focusing on a drug called LGD-4033, which is a selective androgen receptor modulator (SARM). SARMs are performance enhancing drugs that are used in sports but administered without medical supervision could lead to damaging side-effects. This study aims to generate data on the metabolism of LGD-4033 in horses that would assist doping control laboratories in their anti-doping efforts.

Methodology

  • The researchers orally administered LGD-4033 to two Thoroughbred horses and collected samples of urine, plasma (blood without cells), and hair for analysis.
  • A method called LC-HRMS (liquid chromatography–high resolution mass spectrometry) was utilized to identify the metabolites or byproducts formed when LGD-4033 is metabolized in the body. Metabolites can be indicative of the presence of a drug.
  • In addition to the live animals, the researchers also incubated LGD-4033 in vitro with equine liver microsomes. This is often done to replicate and study the metabolism process in a lab setting.

Findings

  • The analysis showed the presence of eight metabolites in urine, five of which were only found as phase II conjugates (which means they are the products of the second phase of drug metabolism).
  • The parent compound, LGD-4033, could only be detected in urine and it was present in the form of a “conjugate”, indicating it has undergone a chemical transformation in the body.
  • Plasma analysis revealed seven metabolites including the parent compound, with mono-hydroxylated metabolites providing the longest detection time.
  • Analysis of hair samples also indicated minute quantities of the parent compound and one mono-hydroxylated metabolite.
  • The in vitro study produced 11 phase I metabolites (an indication that it’s from the first phase of drug metabolism), all of which were also observed in the live animals.

Conclusion

The comprehensive analysis of the metabolism of LGD-4033 in horses may provide useful indicators for detection of unauthorized use of LGD-4033 in equine sports. It enables the tracking of its presence in equine urine, plasma, and hair even long after it has been administered, providing doping control labs with crucial insights for anti-doping measures.

Cite This Article

APA
Cutler C, Viljanto M, Hincks P, Habershon-Butcher J, Muir T, Biddle S. (2020). Investigation of the metabolism of the selective androgen receptor modulator LGD-4033 in equine urine, plasma and hair following oral administration. Drug Test Anal, 12(2), 247-260. https://doi.org/10.1002/dta.2719

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 12
Issue: 2
Pages: 247-260

Researcher Affiliations

Cutler, Charlotte
  • LGC, Fordham, Cambridgeshire, UK.
Viljanto, Marjaana
  • LGC, Fordham, Cambridgeshire, UK.
Hincks, Pamela
  • LGC, Fordham, Cambridgeshire, UK.
Habershon-Butcher, Jocelyn
  • British Horseracing Authority, London, UK.
Muir, Tessa
  • British Horseracing Authority, London, UK.
Biddle, Simon
  • LGC, Fordham, Cambridgeshire, UK.

MeSH Terms

  • Administration, Oral
  • Animal Fur / chemistry
  • Animal Fur / metabolism
  • Animals
  • Doping in Sports
  • Horses / blood
  • Horses / metabolism
  • Horses / urine
  • Nitriles / administration & dosage
  • Nitriles / blood
  • Nitriles / metabolism
  • Nitriles / urine
  • Performance-Enhancing Substances / administration & dosage
  • Performance-Enhancing Substances / blood
  • Performance-Enhancing Substances / metabolism
  • Performance-Enhancing Substances / urine
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / blood
  • Pyrrolidines / metabolism
  • Pyrrolidines / urine
  • Receptors, Androgen / metabolism
  • Substance Abuse Detection / methods
  • Tandem Mass Spectrometry / methods

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Citations

This article has been cited 4 times.
  1. Breuer J, Thomas A, Delahaut P, Schänzer W, Geyer H, Thevis M. Investigations into the concentration and metabolite profiles of stanozolol and LGD-4033 in blood plasma and seminal fluid using liquid chromatography high-resolution mass spectrometry. Anal Bioanal Chem 2023 Feb;415(4):669-681.
    doi: 10.1007/s00216-022-04456-ypubmed: 36441233google scholar: lookup
  2. Wagener F, Guddat S, Görgens C, Angelis YS, Petrou M, Lagojda A, Kühne D, Thevis M. Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes. Anal Bioanal Chem 2022 Jan;414(2):1151-1162.
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  3. Angelis YS, Sakellariou P, Thevis M, Thomas A, Petrou M, Pitsinos EN. Further Insights Into the Metabolism of LGD-4033 in Human Urine. Part 1. Structure Elucidation of Additional Important Metabolites. Drug Test Anal 2026 Feb;18(2):245-259.
    doi: 10.1002/dta.70009pubmed: 41367083google scholar: lookup
  4. Angelis YS, Sakellariou P, Keiler AM, Thevis M, Thomas A, Lam K, Wolber G, Vonaparti A, Voss S, Petrou M, Pitsinos EN. Further Insights Into the Metabolism of LGD-4033 in Human Urine. Part 2. A New Minor Metabolite With Antagonistic Activity on the Androgen Receptor Can Indicate Recent Substance Intake. Drug Test Anal 2026 Jan;18(1):159-169.
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