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Drug testing and analysis2024; doi: 10.1002/dta.3643

Detection of FG-4592 and metabolites in equine plasma, urine and hair following oral administration.

Abstract: FG-4592 is a hypoxia-inducible factor inhibitor that has been approved for therapeutic use in some countries. This class of compounds can increase the oxygen carrying capacity of the blood and thus have the potential to be used as performance enhancing agents in sports. The purpose of this study was to investigate the detection of FG-4592 and metabolites in equine plasma and mane hair following a multiple dose oral administration to two Thoroughbred racehorses, to identify the best analytical targets for doping control laboratories. Urine samples were also analysed, and the results compared to previously published urine data. Liquid chromatography-high resolution mass spectrometry was used for metabolite identification in urine and plasma. Liquid chromatography-tandem mass spectrometry was used for full sample analysis of urine, plasma and hair samples and generation of urine and plasma profiles. FG-4592 and a mono-hydroxylated metabolite were detected in plasma. FG-4592 was detected with the greatest abundance and gave the longest duration of detection, up to 312 h post-administration, and would be the recommended target in routine doping samples. FG-4592 was detected in all mane hair samples collected post-administration, up to 166 days following the final dose, showing extended detection can be achieved with this matrix. To the best of the authors' knowledge, this is the first report of FG-4592 and metabolites in equine plasma and hair samples. Urine results were consistent with the previously published data, with FG-4592 offering the best target for detection and longest detection periods.
© 2024 John Wiley & Sons Ltd.
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Publication Date: 2024-01-12 PubMed ID: 38217093DOI: 10.1002/dta.3643Google 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 research paper investigates the presence and detection of a potentially performance-enhancing drug, FG-4592, and its byproducts in racehorses. Using various testing methods, the researchers found that FG-4592 could be detected in a horse’s plasma, urine, and hair for extended periods following its use.

Introduction to FG-4592 and Its Potential for Misuse

  • The study begins by discussing FG-4592, a hypoxia-inducible factor inhibitor. This is a type of drug that can increase the blood’s ability to carry oxygen.
  • This capability makes FG-4592 and similar substances potential performance enhancing drugs in sports, as higher oxygen-carrying capacity can improve an athlete’s— or a racehorse’s— stamina.

Purpose and Methodology of the Research

  • The research’s purpose was to explore the detection of FG-4592 and its metabolites— the substances produced when a body metabolizes or breaks down a drug— in equine (horse) plasma and mane hair.
  • The researchers administered multiple oral doses of FG-4592 to two Thoroughbred racehorses.
  • They then used liquid chromatography-high resolution mass spectrometry—a technique that provides information about a compound’s weight, accuracy and precision—to identify metabolites in the horse’s urine and plasma. Liquid chromatography-tandem mass spectrometry, which uses two mass spectrometers in sequence, was used for sample analysis and comparing urine and plasma profiles.
  • While analyzing these samples, the researchers also compared their findings to previously published urine data.

Findings about FG-4592’s Presence in Horses

  • FG-4592 and a mono-hydroxylated metabolite—one product of FG-4592’s breakdown in the body—were detected in the horse’s plasma.
  • The researchers found that FG-4592 presented in the greatest abundance and offered the longest period of detection, up to 312 hours following administration. Because of this, they suggest FG-4592 as the best target for examination in routine drug tests.
  • The study also found traces of FG-4592 in all mane hair samples taken after administration, even up to 166 days after the final dose. This implies that tests on hair can detect past use of the drug for quite some time.
  • These results are in line with previously published data on urine samples, further solidifying FG-4592 as the best target for detection tests.

Innovation and Significance of the Research

  • This study constitutes the first report of FG-4592 and its metabolites in equine plasma and hair samples, making it a significant contribution to the field of sports doping control.

Cite This Article

APA
Cutler C, Viljanto M, Taylor P, Hincks P, Habershon-Butcher J, Gray B, Scarth J. (2024). Detection of FG-4592 and metabolites in equine plasma, urine and hair following oral administration. Drug Test Anal. https://doi.org/10.1002/dta.3643

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English

Researcher Affiliations

Cutler, Charlotte
  • LGC Ltd, Fordham, UK.
Viljanto, Marjaana
  • LGC Ltd, Fordham, UK.
Taylor, Polly
  • LGC Ltd, Fordham, UK.
Hincks, Pamela
  • LGC Ltd, Fordham, UK.
Habershon-Butcher, Jocelyn
  • British Horseracing Authority, London, UK.
Gray, Bobby
  • LGC Ltd, Fordham, UK.
Scarth, James
  • LGC Ltd, Fordham, UK.

Grant Funding

  • British Horseracing Authority

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Citations

This article has been cited 1 times.
  1. Checkouri A, Gheddar L, Arbouche N, Raul JS, Kintz P. Simultaneous detection of three hypoxia-inducible factor stabilizers-molidustat, roxadustat, and vadadustat-in multiple keratinized matrices and its application in a doping context. Drug Test Anal 2025 May;17(5):647-654.
    doi: 10.1002/dta.3771pubmed: 38992954google scholar: lookup
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