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In vitro mimicry of metabolic oxidation reactions by electrochemistry/mass spectrometry †
Author(s) -
Jurva Ulrik,
Wikström Håkan V.,
Bruins Andries P.
Publication year - 2000
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/(sici)1097-0231(20000331)14:6<529::aid-rcm904>3.0.co;2-h
Subject(s) - chemistry , mass spectrometry , electrochemistry , hydroquinone , oxidative phosphorylation , drug metabolism , metabolism , chromatography , combinatorial chemistry , biochemistry , electrode
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 ‐2‐thienylethylamino)‐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 p ‐hydroquinone 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. Copyright © 2000 John Wiley & Sons, Ltd.