Metabolite profiling study of propranolol in rat using LC/MS/MS analysis

Abstract

Metabolite profiling is one of the most challenging fields in applied mass spectrometry. Mass spectrometry was used to characterize the metabolites of propranolol, a beta-adrenergic receptor antagonist containing numerous oxidation sites. Propranolol is extensively metabolized, with most metabolites appearing in urine. Urine samples were collected from young adult male Sprague-Dawley rats. Structural identification of various metabolites was performed by LC/MS/MS, using a PE SCIEX triple quadrupole instrument (PE SCIEX API 3000). Metabolites were itemized using several LC/MS/MS techniques, including Q3 full scan and precursor and constant neutral loss experiments. A looped experiment technique revealed the presence of mono- and di-hydroxylated metabolites as well as regio isomers of hydroxy- and dihydroxy-propranolol glucuronides and propranolol glucuronic acid. Propranolol glucuronide was not observed, while the presence of dealkylated metabolites was suggested but not confirmed.