Implementation of the HIF activator IOX-2 in routine doping controls - pilot study data

Early 2020, racehorse doping cases revolved around the hypoxia-inducible factor (HIF) activator IOX-2. While the composition of IOX-2 was known and monitored also in human doping controls since several years, the testing capability of routine sports drug testing methods was revisited concerning this newly surfaced doping agent. IOX-2 and the analytically well-established HIF activator roxadustat (FG-4592) share identical precursor/product ion pairs, enabling co-detection in existing initial testing procedures in routine doping controls considering the intact unconjugated analytes. In addition, hydroxylated IOX-2 and the corresponding glucuronic acid conjugates were identified as major metabolites in a microdose elimination study, contributing to enhanced initial testing and confirmation procedures.

Keywords: HIF activator; IOX-2; LC-MS; human urine; roxadustat; sports drug testing.