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

Christian Görgens1, Sven Guddat1, Christina Bosse1

  • 1Center for Preventive Doping Research/Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.

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|August 19, 2020
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Summary

Hypoxia-inducible factor (HIF) activator IOX-2, a racehorse doping agent, can be detected using existing methods due to shared ion pairs with roxadustat. New metabolites enhance detection capabilities.

Keywords:
HIF activatorIOX-2human urineroxadustatsports drug testing

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Area of Science:

  • * Analytical Chemistry
  • * Biochemistry
  • * Veterinary Pharmacology

Background:

  • * The hypoxia-inducible factor (HIF) activator IOX-2 emerged as a doping agent in racehorses in early 2020.
  • * IOX-2's composition has been known and monitored in human doping controls, prompting a review of its detectability in sports drug testing.
  • * Existing analytical methods for sports drug testing were evaluated for their capability to detect IOX-2.

Purpose of the Study:

  • * To assess the detectability of the hypoxia-inducible factor (HIF) activator IOX-2 in routine doping controls.
  • * To investigate the shared analytical characteristics between IOX-2 and roxadustat (FG-4592).
  • * To identify major metabolites of IOX-2 for improved detection and confirmation procedures.

Main Methods:

  • * Analysis of precursor/product ion pairs shared between IOX-2 and roxadustat (FG-4592).
  • * Application of existing initial testing procedures in routine doping controls.
  • * Identification of hydroxylated IOX-2 and its glucuronic acid conjugates in a microdose elimination study.

Main Results:

  • * IOX-2 and roxadustat (FG-4592) share identical precursor/product ion pairs, allowing co-detection in initial testing for unconjugated analytes.
  • * Hydroxylated IOX-2 and its glucuronic acid conjugates were identified as major metabolites.
  • * The shared analytical properties and identified metabolites enhance the capabilities of initial testing and confirmation procedures.

Conclusions:

  • * Existing doping control methods are capable of co-detecting IOX-2 and roxadustat due to shared ion pairs.
  • * The identification of IOX-2 metabolites provides crucial information for developing more robust and sensitive detection strategies.
  • * These findings contribute to enhanced anti-doping efforts in equine sports by improving the detection of HIF activators.