Nonaqueous capillary electrophoresis as separation technique to support metabolism studies by means of electrochemistry and mass spectrometry

The first combination of electrochemistry (EC), NACE, and ESI-MS to mimic the metabolic fate of drugs is described. While the combination of EC, HPLC, and ESI-MS has been used for this purpose before, NACE is able to deliver valuable additional information about possible metabolites of harmane when compared to HPLC. In this paper, NACE is used as a comprehensive separation technique in metabolism studies of harmane, a naturally occurring monoaminooxidase inhibitor, since it exhibits beneficial properties for the separation of polar compounds. Harmane is known to be metabolized via the oxidative metabolism catalyzed by cytochrome P450 enzymes, which are the most important metabolizing superfamily of enzymes in the human liver. The application of HPLC and NACE enabled the detection of 37 products in total, with 14 different mass-to-charge ratios. A total of 31 products could be detected in HPLC-MS and 26 in NACE-MS analysis. The combination of both NACE and RP-HPLC allows the identification of significantly more potential metabolites than any of the separation techniques alone.