The New Panacea in Metabolomics, Proteomics and Genomics - Electrochemistry/Mass Spectrometry

RP-65 Combining Electrochemistry (EC) with Mass Spectrometry (MS) has shown great potential for the investigation of drug metabolism1,2,3. Recently, the use of EC/MS has been extended towards new applications such as: 1. Fast synthesis of metabolites in micro preparative mode to generate sufficient amounts for the characterization by NMR and/or use as reference material. A specially designed μ-preparative electrochemical flow cell will be presented. 2. Rapid risk assessments of drug-protein binding. Investigation of drug-protein adducts by conventionally used techniques (microsomal incubation, in-vivo studies) are very laborious and have often low efficiency. With the application of EC, it is possible to activate proteins and drugs within seconds to undergo covalent drug-protein binding. 3. Signal enhancement in MS Proteomics. EC/LC/MS can enhance the signal intensity in MS by using electroactive derivatizing agent (e.g. N-(2-Ferroceneethyl)maleimide (FEM) for stabilizing thiol groups in proteins) or directly improving ionization efficiency. 4. Oxidative damage of DNA. On-line EC/ESI-MS is novel tool to study oxidative processes of nucleic acids, as well as to create covalent drug adducts with nucleic acids. All these applications illustrate the tremendous power and broad applicability of electrochemistry as a promising tool to mimic nature's Redox reactions, including oxidative damage of DNA, protein stress, lipid oxidation, etc. [1] Jurva U., Wikstrom H. V., Weidolf L., Bruins A.P., Comparison between electrochemistry/mass spectrometry and cytochrome P450 catalyzed oxidation reactions, Rapid Commun. Mass Spectrom. 17 (2003) 800–810. [2] Baumann A., Lohmann W., Schubert B., Oberacher H., Karst U., Metabolic studies of tetrazepam based on electrochemical simulation incomparison to in vivo and in vitro methods, J. Chromatogr. A 1216 (2009) 3192–3198. [3] Lohmann W., Hayen H., Karst U.,Covalent Protein Modification by Reactive Drug Metabolites Using Online Electrochemistry/LiquidChromatography/Mass Spectrometry, Anal. Chem. 80 (2008) 9714–9719.