Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent: Investigation on a positive case

Detection by LC-MS/MS of HIF stabilizer FG-4592 used as a new doping agent : Investigation on a positive case / C. Buisson, A. Marchand, I. Bailloux, A. Lahaussois, L. Martin, A. Molina

  • Journal of Pharmaceutical and Biomedical Analysis 121 (20 March 2016), p. 181-187
  • PMID: 26808067
  • DOI: 10.1016/j.jpba.2016.01.029


Stabilizing the labile factor HIF (hypoxia inducible factor) for therapeutic use has led to the development of various molecules by pharmaceutical companies. These HIF stabilizers show promising erythropoiesis stimulating capacities and are of great interest for patients with chronical kidney disease and anemia. Amongst them FG-4592 from FibroGen is now under phase 3 of clinical studies. While this drug is still under investigation, a parallel market already allows to buy this product, which could be tempting for some athletes willing to increase their performances. To avoid such a use for doping purpose, WADA has listed HIF stabilizers and FG-4592 in particular as prohibited substances since 2011 and some anti-doping laboratories have developed a technique of identification of FG-4592 in urine. Here, we described the first case ever identified by an anti-doping laboratory of an athlete using FG-4592. Detection and confirmation in urinary samples was performed by LC-MS/MS. In addition, potential indirect markers erythropoietin (EPO) and hematological parameters followed in the Athlete Biological Passport (ABP) were analyzed during and after the period of use but showed no profound alterations. Only ABPS (abnormal blood profile score) reached (but did not exceed) the upper limit proposed by the ABP adaptive model just after the period of use of FG-4592. Altogether this case sends a warning for anti-doping laboratories which now must strengthen surveillance on HIF stabilizers and develop sensitive methods of detection for this new class of drugs.


Case report
Research / Study
15 January 2016
Bailloux, I.
Buisson, Corinne
Lahaussois, A.
Marchand, Alexandre
Martin, Laurent
Molina, A.
Adverse Analytical Finding / presence
Paris, France: Agence Française de Lutte contre le Dopage (AFLD)
Analytical aspects
Mass spectrometry analysis
Testing method development
Doping classes
S2. Peptide Hormones, Growth Factors
Hypoxia-inducible factor (HIF) activating agents
Roxadustat (FG-4592)
Athlete Biological Passport (ABP)
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Date generated
1 November 2022
Date of last modification
16 November 2022
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