Equine metabolic investigation of the phosphodiesterase-4 inhibitor ibudilast as a potential performance enhancer

  • Rapid Commun Mass Spectrom. 2024 Dec 15;38(23):e9916. doi: 10.1002/rcm.9916.
Moses Philip  1 ,  Abdul Khader Karakka Kal  1 ,  Michael Benedict Subhahar  1 ,  Tajudheen K Karatt  1 ,  Fatma Mohammed Graiban  1 ,  Meleparappil Muhammed Ajeebsanu  1 ,  Marina Joseph  2 ,  Shantymol V Jose  2
Affiliations
  • 1. Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
  • 2. Department of Bacteriology, Diagnostic Section, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
PMID: 39307998 DOI: 10.1002/rcm.9916
Abstract

Rationale: Phosphodiesterase 4 (PDE4) inhibitors are a newer class of drugs that induce bronchodilation and have anti-inflammatory effects, making them susceptible to misuse as performance enhancers in competitive sports.

Methods: This study explores the metabolic conversion of PDE4 Inhibitor ibudilast in thoroughbred horses after oral administration and in vitro using equine liver microsomes and Cunninghamella elegans. A liquid chromatography-high resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites.

Results: A total of 20 in vivo metabolites were identified under experimental conditions, including 12 Phase I and 8 Phase II conjugated metabolites. Phase I metabolites were predominantly formed through hydroxylation (mono-, di-, and tri-hydroxylation). Demethylated metabolites were also identified during this investigation. Additionally, the research detected Phase II metabolites conjugated with glucuronic and sulfonic acids.

Conclusions: The data presented here can assist in detecting the PDE4 Inhibitor ibudilast and uncover its illicit use in competitive sports.

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