Comprehensive insights into the formation of metabolites of the ghrelin mimetics capromorelin, macimorelin and tabimorelin as potential markers for doping control purposes

Comprehensive insights into the formation of metabolites of the ghrelin mimetics capromorelin, macimorelin and tabimorelin as potential markers for doping control purposes / Tobias Lange, Andreas Thomas, Christian Görgens, Martin Bidlingmaier, Katharina Schilbach, Eric Fichant, Philippe Delahaut, Mario Thevis. - (Biomedical Chromatography (2021) 17 January; p. 1-18)

  • PMID: 33458843
  • DOI: 10.1002/bmc.5075


Abstract

Analytical methods to determine the potential misuse of the ghrelin mimetics capromorelin (CP-424,391), macimorelin (macrilen, EP-01572) and tabimorelin (NN703) in sports were developed. Therefore, different extraction strategies, i.e. solid-phase extraction, protein precipitation, as well as a "dilute-and-inject" approach, from urine and EDTA-plasma were assessed and comprehensive in vitro/in vivo experiments were conducted, enabling the identification of reliable target analytes by means of high resolution mass spectrometry. The drugs' biotransformation led to the preliminary identification of 51 metabolites of capromorelin, 12 metabolites of macimorelin and 13 metabolites of tabimorelin. Seven major metabolites detected in rat urine samples collected post-administration of 0.5-1.0 mg of a single oral dose underwent in-depth characterization, facilitating their implementation into future confirmatory test methods. In particular, two macimorelin metabolites exhibiting considerable abundances in post-administration rat urine samples were detected, which might contribute to an improved sensitivity, specificity, and detection window in case of human sports drug testing programs. Further, the intact drugs were implemented into World Anti-Doping Agency-compliant initial testing (limits of detection 0.02-0.60 ng/ml) and confirmation procedures (limits of identification 0.18-0.89 ng/ml) for human urine and blood matrices. The obtained results allow extension of the test spectrum of doping agents in multitarget screening assays for growth hormone-releasing factors from human urine.

Original document

Parameters

Science
Study
Date
14 January 2021
People
Bidlingmaier, Martin
Delahaut, Philippe
Fichant, Eric
Görgens, Christian
Lange, Tobias
Schilbach, Katharina
Thevis, Mario
Thomas, Andreas
Country
Belgium
Germany, Democratic Republic of (1949-1990)
Language
English
Other organisations
Département Santé du CER Groupe (Laboratoire d’Hormonologie) - Health Department of the CER Group
Deutsche Sporthochschule Köln (DSHS) - German Sport University Cologne
European Monitoring Center for Emerging Doping Agents (EuMoCEDA)
Klinikum der Universität München (LMU Klinikum)
Ludwig-Maximilians-Universität München (LMU) - Ludwig Maximilian University of Munich
Analytical aspects
Mass spectrometry analysis
Metabolization
Testing method development
Doping classes
S2. Peptide Hormones, Growth Factors
Substances
Growth Hormone Releasing Peptide (GHRP)
Lenomorelin
Macimorelin
Tabimorelin
Document category
Scientific article
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Pdf file
Date generated
22 February 2021
Date of last modification
3 March 2021
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  • Education
  • Science
  • Statistics
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  • ADRV
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  • Analytical aspects
  • Doping classes
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