Universität zu Köln

Krombholz, Sophia, Thomas, Andreas ORCID: 0000-0003-1199-0743 and Thevis, Mario (2022). Investigations into the In Vitro Metabolism of hGH and IGF-I Employing Stable-Isotope-Labelled Drugs and Monitoring Diagnostic Immonium Ions by High-Resolution/High-Accuracy Mass Spectrometry. Metabolites, 12 (2). BASEL: MDPI. ISSN 2218-1989

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Abstract

Studying the metabolism of prohibited substances is an essential element in anti-doping research in order to facilitate and improve detectability. Whilst pharmacokinetic studies on healthy volunteers are valuable, they are often difficult, not least due to safety reasons and ethical constraints, especially concerning peptidic substances, which must be administered parenterally. Hence, there is a growing need for suitable in vitro models and sophisticated analytical strategies to investigate the metabolism of protein- and peptide-derived drugs. These include human growth hormone (hGH) and its main mediator insulin-like growth factor-I (IGF-I), both prohibited in professional sports for their anabolic and lipolytic effects, while challenging in their detection, as they occur naturally in the human body.Within this study, the in vitro metabolism of hGH and IGF-I was investigated using a stable-isotope-labelled reporter ion screening strategy (IRIS). A combination of liquid chromatography, high-resolution mass spectrometry, and characteristic immonium ions generated by internal dissociation of the stable-isotope-labelled peptidic metabolites enabled the detection of specific fragments. Several degradation products for hGH and IGF-I were identified within this study. These metabolites, potentially even indicative for subcutaneous administration of the drugs, could serve as promising targets for the detection of hGH and IGF-I misuse in future anti-doping applications.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Krombholz, Sophia UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-665843
DOI:	10.3390/metabo12020146
Journal or Publication Title:	Metabolites
Volume:	12
Number:	2
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2218-1989
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-HORMONE; PEPTIDE-HORMONES; INSULIN; ABUSE; CHALLENGES; URINE; SERUM Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66584