In vitro mimicry of metabolic oxidation reactions by electrochemistry/massspectrometry

The aim of these studies was to investigate the scope and limitations of el ectrochemistry on-line with mass spectrometry as a quick and convenient way to mimic phase I:oxidative reactions in drug metabolism. A compound with p reviously reported in vitro and in vivo metabolism, the dopamine agonist 2- (N-propyl-N-2-thienylethylamino)-5-hydroxytetralin, was examined in an elec trochemistry/mass spectrometry (EC/MS) system. The previously reported N-de alkylation was mimicked by the electrochemical cell while the oxidation of the phenol function was not fully mimicked by the EC/MS system, since the c atechol and p-hydroquinone formed were immediately oxidized to the correspo nding quinones, Since cytochrome P450 isoenzymes are the most important enz ymes in phase I oxidative metabolism, two standard substrates used for the characterization of those enzymes, lidocaine and 7-ethoxycoumarin, were tes ted in the EC/MS system. The electrochemical cell was capable of mimicking the N-dealkylation of lidocaine but, under the conditions used in our exper iments, the O-deethylation of 7-ethoxycoumarin could not be simulated in th e electrochemical cell. Copyright (C) 2000 John Whey & Sons, Ltd.