Identification of human in vitro metabolites of the haemoglobin S polymerization inhibitor voxelotor for doping control purposes

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Sebastian Rzeppa - (Erstautor:in)
  • Sven Voss - , Institut für Dopinganalytik und Sportbiochemie Dresden (Autor:in)
  • Detlef Thieme - , Institut für Dopinganalytik und Sportbiochemie Dresden (Autor:in)
  • Annekathrin Keiler - , Umweltmonitoring und Endokrinologie (FoG), Institut für Dopinganalytik und Sportbiochemie Dresden (Letztautor:in)


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.


FachzeitschriftDrug Testing and Analysis
PublikationsstatusVeröffentlicht - 16 Mai 2023

Externe IDs

unpaywall 10.1002/dta.3489
Scopus 85159382826
WOS 000987538300001
ORCID /0000-0002-2157-4711/work/142251667


Ziele für nachhaltige Entwicklung


  • GBT440, HPLC-MS/MS, HRMS, biotransformation, doping, Hrms, Gbt440, Biotransformation, Ms, Doping, Hplc-ms