Comprehensive insights into the formation of metabolites of the ghrelin mimetics capromorelin, macimorelin and tabimorelin as potential markers for doping control purposes.
Biomed Chromatogr
; 35(6): e5075, 2021 Jun.
Article
in En
| MEDLINE
| ID: mdl-33458843
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Piperidines
/
Pyrazoles
/
Tryptophan
/
Dipeptides
/
Doping in Sports
/
Indoles
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
/
Male
Language:
En
Journal:
Biomed Chromatogr
Year:
2021
Document type:
Article
Affiliation country: