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Drug testing and analysis2021; 13(6); 1191-1202; doi: 10.1002/dta.3013

Comprehensive characterization of the peroxisome proliferator activated receptor-δ agonist GW501516 for horse doping control analysis.

Abstract: According to international sport institutions, the use of peroxisome proliferator activated receptor (PPAR)-δ agonists is forbidden at any time in athlete career due to their capabilities to increase physical and endurance performances. The (PPAR)-δ agonist GW501516 is prohibited for sale but is easily available on internet and can be used by cheaters. In the context of doping control, urine is the preferred matrix because of the non-invasive nature of sampling and providing broader exposure detection times to forbidden molecules but often not detected under its native form due to the organism's metabolism. Even if urinary metabolism of G501516 has been extensively studied in human subjects, knowledge on GW501516 metabolism in horses remains limited. To fight against doping practices in horses' races, GW501516 metabolism has to be studied in horse urine to identify and characterize the most relevant target metabolites to ensure an efficient doping control. In this article, in vitro and in vivo experiments have been conducted using horse S9 liver microsome fractions and horse oral administration route, respectively. These investigations determined that the detection of GW501516 must be performed in urine on its metabolites because the parent molecule was extremely metabolized. To maximize analytical method sensitivity, the extraction conditions have been optimized. In accordance with these results, a qualitative analytical method was validated to detect the abuse of GW501516 based on its most relevant metabolites in urine. This work enabled the Laboratoire des Courses Hippiques (LCH) to highlight two cases of illicit administration of this forbidden molecule in post-race samples.
© 2021 John Wiley & Sons, Ltd.
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Publication Date: 2021-02-11 PubMed ID: 33547737DOI: 10.1002/dta.3013Google 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 paper explores the comprehensive characterization of the peroxisome proliferator activated receptor-delta (PPAR-δ) agonist GW501516 for horse doping control analysis. It basically focuses on optimizing methods for detection of GW501516 metabolites in horse urine for efficient anti-doping procedures.

Background and Purpose

  • PPAR-δ agonists, like GW501516, are enhancements that improve physical and endurance performance.
  • Although these substances are prohibited in competitive sports, they are conveniently available online and, hence, accessible to cheaters. This means there’s a need for effective detection methods.
  • The authors chose urine as the preferred sampling medium because of its non-invasive nature and it offers broader exposure detection times to prohibited substances.

Methodology

  • In order to understand how GW501516 behaves in horses, both in vitro and in vivo experiments were conducted using horse’s S9 liver microsome fractions and horse oral administration route respectively.
  • The researchers investigated how GW501516 gets metabolized in the horse’s body and how to identify the relevant metabolites in urine samples.

Findings

  • The study found that the detection of GW501516 had to be carried out on its metabolites in urine because the parent molecule was extensively metabolized.
  • To increase the sensitivity of the analytical method, the extraction conditions were optimized.
  • A qualitative analytical method was then validated based on its most relevant metabolites in urine to detect the abuse of GW501516.

Impact of the Research

  • Due to the findings of this research, the Laboratoire des Courses Hippiques (LCH) was able to detect two cases of illegal use of GW501516 in post-race samples.
  • The outcome of this research helps in furthering efforts to curb doping practices in horse racing.

Cite This Article

APA
Trevisiol S, Moulard Y, Delcourt V, Jaubert M, Boyer S, Tendon S, Haryouli H, Taleb W, Caroff M, Chabot B, Drif L, André F, Garcia P, Loup B, Popot MA, Bailly-Chouriberry L. (2021). Comprehensive characterization of the peroxisome proliferator activated receptor-δ agonist GW501516 for horse doping control analysis. Drug Test Anal, 13(6), 1191-1202. https://doi.org/10.1002/dta.3013

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 13
Issue: 6
Pages: 1191-1202

Researcher Affiliations

Trevisiol, Stéphane
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Moulard, Yves
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Delcourt, Vivian
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Jaubert, Murielle
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Boyer, Sophie
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Tendon, Sophie
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Haryouli, Hayate
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Taleb, Wafek
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Caroff, Mylène
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Chabot, Benjamin
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Drif, Laura
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
André, François
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Garcia, Patrice
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Loup, Benoit
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Popot, Marie-Agnès
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.
Bailly-Chouriberry, Ludovic
  • GIE-LCH, Laboratoire des Courses Hippiques, Verrières-le-Buisson, France.

MeSH Terms

  • Administration, Oral
  • Animals
  • Doping in Sports / prevention & control
  • Female
  • Horses
  • Male
  • Microsomes, Liver / metabolism
  • PPAR delta / agonists
  • Substance Abuse Detection / methods
  • Thiazoles / analysis
  • Thiazoles / metabolism
  • Thiazoles / urine

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Citations

This article has been cited 3 times.
  1. Sibille B, Mothe-Satney I, Le Menn G, Lepouse D, Le Garf S, Baudoin E, Murdaca J, Moratal C, Lamghari N, Chinetti G, Neels JG, Rousseau AS. Gene Doping with Peroxisome-Proliferator-Activated Receptor Beta/Delta Agonists Alters Immunity but Exercise Training Mitigates the Detection of Effects in Blood Samples. Int J Mol Sci 2021 Oct 25;22(21).
    doi: 10.3390/ijms222111497pubmed: 34768927google scholar: lookup
  2. Turza A, Bosca M, Muresan-Pop M, Mare L, Borodi G, Popescu V. Novel Solid Forms of Cardarine/GW501516 and Their Characterization by X-Ray Diffraction, Thermal, Computational, FTIR, and UV Analysis. Pharmaceutics 2025 Jan 23;17(2).
    doi: 10.3390/pharmaceutics17020152pubmed: 40006519google scholar: lookup
  3. Turza A, Pascuta P, Muresan-Pop M, Mare L, Borodi G, Popescu V. Five Novel Polymorphs of Cardarine/GW501516 and Their Characterization by X-ray Diffraction, Computational Methods, Thermal Analysis and a Pharmaceutical Perspective. Pharmaceutics 2024 May 7;16(5).
    doi: 10.3390/pharmaceutics16050623pubmed: 38794285google scholar: lookup
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