title: In vitro mimicry of metabolic oxidation reactions by electrochemistry/mass spectrometry.
abstract: 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.
authors.affiliation: University of Groningen, Centre for Pharmacy, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: U
authors.initials: U
authors.lastname: Jurva
authors.forename: H V
authors.initials: HV
authors.lastname: Wikström
authors.forename: A P
authors.initials: AP
authors.lastname: Bruins
mesh_terms: D000779:Anesthetics, Local / Q000378:metabolism; D000818:Animals; D003640:Dealkylation; D018491:Dopamine Agonists / Q000378:metabolism; D004563:Electrochemistry; D066298:In Vitro Techniques; D008012:Lidocaine / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D013876:Thiophenes / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D018491:Dopamine Agonists; D004364:Pharmaceutical Preparations; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine; D008012:Lidocaine