CHARACTERIZATION OF IN VIVO PLASMA METABOLITES OF TEPOXALIN IN HORSES USING LC-MS-MS

Tepoxalin is a veterinary drug registered for use in the dog as a dual inhibitor (cyclooxygenase - 5 lipoxygenase). In the horse, it predominantly triggers a strong cyclooxygenase inhibition; this bias seems to be due to the action of its metabolite(s). Among these, only the RWJ-20142 is well known, while to the best of our knowledge no information is available on the other metabolites produced in vivo. Hence, the identification of its main metabolic pathway is pivotal to better understand its clinical activity. A suitable high performance liquid chromatography method has been applied to liquid chromatography–mass spectrometry for the characterization of the main metabolites in plasma of horses orally treated with tepoxalin. Mass spectrometry in full scan, product ion scan and precursor ion scan modes, provided information useful in elucidating large parts of the structure of the unknown metabolites detected. These structures are closely related to that of tepoxalin. One of these metabolites was speculated to be a structural isomer of the parental drug. These findings could be important to understand the pharmacology of tepoxalin in horses.