Electrochemistry-mass spectrometry to study reactive drug metabolites and CYP450 simulations

The use of electrochemistry (EC) coupled to mass spectrometry (MS) has been widely reported in the past two decades as a tool for simulating drug metabolism. EC-MS is now used to generate metabolites in a simple matrix with easy implementation for high-throughput analysis. Another interesting use of EC in drug-metabolism investigation is simulation of the formation of reactive drug metabolites. Electrochemical reactions tend to be limited to the simulation of single-electron transfers initiated by cytochrome P450 reactions, hence the need for new analytical developments. This review aims to describe current knowledge of the use of EC-MS for the generation and the identification of reactive drug metabolites. We detail the electrochemical formation of electrophilic aryl, nitroso, aromatics and nitrogen-oxide species in the first part. We give future perspectives related to the surface-modified electrode coupled with MS for inhibition.