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Characterization of Novel Metabolites of the HIF Stabilizer JNJ-42041935 in Rats Using LC-HRMS for Doping Control Purposes: A Pilot Study
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DOI：10.1002/dta.70086.png)
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Abstract
En 中文
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) stimulate erythropoiesis and enhance performance, and were banned by the World Anti-Doping Agency in the year 2011. JNJ-42041935, a potent and selective PHD inhibitor, was administered orally to Sprague–Dawley rats, and its metabolites were tentatively characterized using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) in positive and negative ionization modes. Eleven metabolites were identified, with Phase I reactions including monohydroxylation, dechlorination, and decarboxylation, and Phase II reactions comprising methylation, glucuronidation, sulfation, glycine, and taurine conjugation. These results provide insights into JNJ-42041935 biotransformation and support the development of analytical methods for HIF-PHI detection in anti-doping control. Future studies will continue to identify and characterize the valuable metabolites of JNJ-42041935, with a view to providing a more comprehensive understanding of its in vivo metabolic profile and developing improved detection methods.
Keywords:
doping control
hypoxia-inducible factor
JNJ-42041935
liquid chromatography-high-resolution mass spectrometry (LC-HRMS)
prolyl-hydroxylase inhibitors
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