Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes

Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes / Felicitas Wagener, Sven Guddat, Christian Görgens, Yiannis S. Angelis, Michael Petrou, Andreas Lagojda, Dirk Kühne, Mario Thevis. - (Analytical and Bioanalytical Chemistry (2021) 4 November)

  • PMID: 34734312
  • DOI: 10.1007/s00216-021-03740-7


Abstract

LGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated dietary supplements (DS). Thus, the urgency to develop methods to differentiate between inadvertent doping and abuse of SARMs to benefit from the performance-enhancing effect of the compound in sports is growing. To gain a better understanding of the metabolism and excretion patterns of LGD-4033, human micro-dose excretion studies at 1, 10, and 50 µg LGD-4033 were conducted. Collected urine samples were prepared for analysis using enzymatic hydrolysis followed by solid-phase extraction and analyzed via LC-HRMS/MS. Including isomers, a total of 15 phase I metabolites were detected in the urine samples. The LC-HRMS/MS method was validated for qualitative detection of LGD-4033, allowing for a limit of detection (LOD) of 8 pg/mL. The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management.

Original document

Parameters

Date
4 November 2021
People
Angelis, Yanis S.
Görgens, Christian
Guddat, Sven
Kühne, Dirk
Lagojda, Andreas
Petrou, Michael
Thevis, Mario
Wagener, Felicitas
Country
Cyprus
Germany
Greece
Language
English
Other organisations
Cyprus Anti-Doping Authority (CyADA)
Deutsche Sporthochschule Köln (DSHS) - German Sport University Cologne
European Monitoring Center for Emerging Doping Agents (EuMoCEDA)
Laboratories
Athens, Greece: Doping Control Laboratory of Athens
Analytical aspects
Mass spectrometry analysis
Metabolization
Testing method development
Doping classes
S1. Anabolic Agents
Substances
LGD-4033 (ligandrol)
Selective androgen receptor modulators (SARMs)
Document category
Scientific article
Document type
Pdf file
Date generated
11 November 2021
Date of last modification
17 November 2021
Category
  • Legal Source
  • Education
  • Science
  • Statistics
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  • Country
  • Language
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  • ADRV
  • Legal Terms
  • Sport/IFs
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  • Laboratories
  • Analytical aspects
  • Doping classes
  • Substances
  • Medical terms
  • Various
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