Comprehensive Drug Metabolism Using Electrochemistry-MS (EC-MS)

Fast mimicking and prediction of oxidative metabolism “in electro” as a comprehensive technique to analyze in vivo and in vitro drug metabolism

So far, most drug metabolism studies have been based on traditional in vitro techniques initially using liver microsomes, and at later stages in vivo techniques using rodents and finally human.

Both techniques are time-consuming and can be very costly. In addition, they require isolation from the biological matrix (i.e., microsomes, urine, plasma) with the risk of sample loss due to adsorption and/or binding to the cell membrane or constituents. Furthermore, conjugation reactions (Phase II reactions), such as adduct formation with glutathione, are difficult to perform in a controlled manner.

Recently, it has been shown that drug metabolites are formed instantaneously in an electrochemical cell, thereby mimicking the enzymatic Cytochrome P450 reactions that usually take place in the liver (Phase I reactions). By on-line coupling of an electrochemical reactor cell with MS (EC-MS) a drug compound can be easily oxidized in a precise and controlled manner within a few minutes, mimicking/predicting the oxidative drug metabolism to become a true biomimetic tool for enzymatic REDOX reactions.