Metabolism and excretion of piperonyl butoxide in the rat

[C-14]-piperonyl butoxide (PBO) was administered to male and female rats by gavage at a dose rate of 50 or 500mgkg(-1) body weight. In all cases, the radioactivity was rapidly excreted with 87-99% being found in the 0-48-h excreta and the majority of the dose (64.1-85.0%) being eliminated in faeces. The metabolism of PBO was complex with over 25 peaks of radioactivity being seen by radio-high-performance liquid chromatography (HPLC). Using HPLC/tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR), 12 urine metabolites were assigned structures together with four plus PBO in faeces. Metabolism occurred at two sites: the methylenedioxy ring, which opened to form a catechol that could then undergo methylation, and the 2-(2-butoxyethoxy) ethoxymethyl side-chain, which underwent sequential oxidation to a series of alcohols and acids. The identified metabolites accounted for approximately 60% of the administered dose.