In vitro mimicry of metabolic oxidation reactions by electrochemistry/mass spectrometry

✍ Scribed by Ulrik Jurva; Håkan V. Wikström; Andries P. Bruins

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 75 KB
• Volume: 14
• Category: Article
• ISSN: 0951-4198
• DOI: 10.1002/(sici)1097-0231(20000331)14:6<529::aid-rcm904>3.0.co;2-h

✦ Synopsis

The aim of these studies was to investigate the scope and limitations of electrochemistry on-line with mass spectrometry as a quick and convenient way to mimic phase I oxidative reactions in drug metabolism. A compound with previously reported in vitro and in vivo metabolism, the dopamine agonist 2-(N-propyl-N-2thienylethylamino)-5-hydroxytetralin, was examined in an electrochemistry/mass spectrometry (EC/MS) system. The previously reported N-dealkylation was mimicked by the electrochemical cell while the oxidation of the phenol function was not fully mimicked by the EC/MS system, since the catechol and phydroquinone formed were immediately oxidized to the corresponding quinones. Since cytochrome P450 isoenzymes are the most important enzymes in phase I oxidative metabolism, two standard substrates used for the characterization of those enzymes, lidocaine and 7-ethoxycoumarin, were tested in the EC/MS system. The electrochemical cell was capable of mimicking the N-dealkylation of lidocaine but, under the conditions used in our experiments, the O-deethylation of 7-ethoxycoumarin could not be simulated in the electrochemical cell.