- Titel
- Identification of human in vitro metabolites of the haemoglobin S polymerization inhibitor voxelotor for doping control purposes
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-927849
- Quellenangabe
- Drug testing and analysis
Erscheinungsjahr: 2023
Jahrgang: 15
Heft: 11-12
Seiten: 1403-1409
E-ISSN: 1942-7611 - Erstveröffentlichung
- 2023
- Abstract (EN)
- Voxelotor (GBT440) is a haemoglobin S polymerization inhibitor used to treat anaemia in sickle cell disease. Due to an increase of arterial oxygen saturation as well as serum erythropoietin and haemoglobin, the World Anti-Doping Agency included voxelotor in the list of prohibited substances and methods in 2023. The objective of the present study was to identify and characterize metabolites of voxelotor to detect a potential misuse by athletes. The biotransformation was studied in vitro using the human hepatocellular cell line HepG2 and pooled human liver microsomes. The metabolites were analysed using high-performance liquid chromatography (high-resolution) mass spectrometry. In total, three phase I metabolites and six phase II metabolites (resulting from glucuro-conjugation and O-methylation) were formed by the HepG2 cells in a time-dependent manner, and two phase I metabolites were generated by the liver microsomes, among them one also found in the HepG2 incubations. A reduced metabolite and the glucuro-conjugate of a reduced metabolite were the most abundant formed by HepG2 cells. In addition, metabolites resulting from mono-hydroxylation, reduction and O-methylation in different combinations were identified. Voxelotor was also found as glucuro-conjugate with a low abundance. With the spectrometric behaviour of voxelotor and its in vitro metabolites described herein, an implementation in doping control screening and, consequently, a detection of an abuse in an athlete urine sample might be possible.
- Andere Ausgabe
- Link zum Artikel der zuerst in der Zeitschrift „Drug testing and analysis” bei Wiley erschienen ist.
DOI: 10.1002/dta.3489 - Freie Schlagwörter (EN)
- biotransformation, doping, GBT440, HPLC-MS/MS, HRMS
- Klassifikation (DDC)
- 610
- Normschlagwörter (GND)
- 796
- Verlag
- Wiley-VCH, Hoboken
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa2-927849
- Veröffentlichungsdatum Qucosa
- 05.08.2024
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY 4.0