Characterization of metabolites of Celecoxib in rabbits by liquid chromatography/tandem mass spectrometry

The metabolism of the anti-inflammatory drug Celecoxib in rabbits was chara cterized using liquid chromatography (LC)/tandem mass spectrometry (MS/MS) with precursor ion and constant neutral loss scans followed by product ion scans, After separation by on-line liquid chromatography, the crude urine s amples and plasma and fecal extracts were analyzed with turbo-ionspray ioni zation in negative ion mode using a precursor ion scan of m/z 69 (CF3) and a neutral loss scan of 176 (dehydroglucuronic acid). The subsequent product ion scans of the [M - H] ions of these metabolites yielded the identificat ion of three phase I and four phase II metabolites. The phase I metabolites had hydroxylations at the methyl group or on the phenyl ring of Celecoxib, and the subsequent oxidation product of the hydroxymethyl metabolite forme d the carboxylic acid metabolite. The phase II metabolites included four po sitional isomers of acyl glucuronide conjugates of the carboxylic acid meta bolite. These positional isomers were caused by the alkaline pH of the rabb it urine and were not found in rabbit plasma. The chemical structures of th e metabolites were characterized by interpretation of their product ion spe ctra and comparison of their LC retention times and the product ion spectra with those of the authentic synthesized standards. Copyright (C) 2000 John Wiley & Sons, Ltd.