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