Abstract
For several years, electrochemistry in combination with mass spectrometry has been the subject of attention and development for studying the oxidative drug metabolism at early stages of new drug development. Though the technique could successfully imitate the in vivo oxidative drug metabolism initiated by electron transfer, it lags in the imitation of reactions initiated by either hydrogen atom transfer or oxygen atom transfer. The prospect of using electrochemistry as a practical analytical technique in the imitation of oxidative drug metabolism, therefore, relies on the extension of its utility toward covering those reactions initiated by hydrogen atom transfer and oxygen atom transfer. In this brief critical review, I discuss potential electrochemical techniques that can benefit the application of electrochemistry beyond electron transfer reactions.
Highlights
Due to the large number of drug candidates at the early stages of new drug development, there is a tangible need for a fast and facile analytical technique to assess the oxidative drug metabolism
Cytochrome P450s are the main family of monooxygenase enzymes that are involved in phase I in vivo oxidative drug metabolism pathways [3]
Cytochrome P450s and their main reactive species, i.e. oxo-ferryl radical cations, promote different oxidative metabolism pathways; namely, those initiated by electron transfer reaction, such as Ndealkylation of tertiary amine moieties, those initiated by hydrogen atom transfer, such as O-dealkylation pathways, and those initiated by oxygen atom transfer such as N-oxidation pathways
Summary
Due to the large number of drug candidates at the early stages of new drug development, there is a tangible need for a fast and facile analytical technique to assess the oxidative drug metabolism. Hyphenated electrochemistry and mass spectrometry technique has been in the center of attention for the last several years to achieve the fast and facile assessment of oxidative drug metabolism at the early stages of new drug development [1,2]. This brief review will present the current status of the technique, and possible efforts to extend its application in a more practical sense in the assessment of oxidative drug metabolism. Interaction of the substrate drug compound with a specific part of the reactive pocket triggers the activation of molecular oxygen in a chain of proton and electron transfer events to generate oxo-ferryl doi:10.5599/admet.2.3.50
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