Electrochemistry has been used with mass spectrometry for a number of years to mimic oxidative metabolism . The combined limitations of the early ionization methods and electrochemical cells of the day made the experiments challenging to conduct on a routine basis. The advent of flowthrough carbon frits as electrodes in electrochemical cells allows simple and reliable set up and conduct of electrochemistry on-line with mass spectrometry. Jurva and co-workers recently conducted a systematic study of the types of oxidation reactions that can be observed for both cytochrome P450 metabolizing enzymes and the flowthrough electrochemical cell . The studies indicate that reactions initiated by a one-electron process such as N-oxidation, S-oxidation, P-oxidation, alcohol oxidation, dehydrogenation, and N-dealkylation are likely to be observed with the electrochemical cell. Reactions thought to involve direct hydrogen atom abstraction such as O-dealkylation and hydroxylation of unsubstituted aromatic rings were not mimicked .
Another use for the on-line electrochemical cell was described by King and co-workers  for the generation and characterization of GSH-drug adducts. The experimental design allowed the oxidation of the drug in the electrochemical cell to be performed in the presence of excess GSH. Reactive intermediates were shown to be effectively trapped by the GSH. The experimental system provides a simple and effective way to generate GSH-drug adducts for characterization by mass spectrometry. Additionally, an experimental design was described that gave information about the potential pathways involved in the formation of GSH-drug adducts. The phase I metabolites from a microso-mal incubation of drug were separated by HPLC and then passed through the on-line electrochemical flow cell along with an infusion of GSH. The reactive species formed by electrochemical oxidation of the metabolites were trapped as GSH conjugates and characterized on-line by mass spectrometry at the chromatographic retention time of the metabolite itself. The formation of acetaminophen by O-dealkylation of phenacetin in microsomes was used as a model system to demonstrate the potential of the approach .
While it is clear that electrochemical reactions represent only a portion of the reactions observed with the cytochrome P450 drug-metabolizing enzymes, electrochemical generation of both phase I and phase II metabolites can be a valuable means for the study of metabolic events, some of which may occur through mechanisms other than the action of cytochrome P450 enzymes.
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