LC/electrochemistry/mass spectrometry in (bio)analytical chemistry, drug metabolism and proteomics

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This proposal comprises four major aspects, which contain the combination of electrochemistry and mass spectrometry as common denominator: Modification of sample molecules with the goal to achieve improved limits of detection and selectivity in mass spectrometry. Electrochemical protein cleavage with respect to the development of an electrochemical alternative to enzymatic digests. Electrochemical oxidation of Pharmaceuticals with the goal to imitate the metabolic pathways occurring in the body and to accelerate in vitro tests for new drug candidates. Miniaturization of electrochemical cells to allow small-scale conversions in a lab-on-a-chip format. For all four aspects, the proofs of principle have already been performed. The research will be focused on the development of new applications in various fields, including proteomics and pharmaceutical analysis based on the combination of liquid chromatography, electrochemistry and mass spectrometry. The applicant and his collaborators at the University of Groningen (The Netherlands), Prof. Rainer Bischoff and Dr. Andries Bruins, and at the Univeristy of Twente (Enschede, The Netherlands), Dr. Wouter Olthuis/Prof. Dr. Albert van den Berg will work on general chemical aspects of this coupling technique: How do the electrochemical processes occur, how can reactions be enabled, which are not possible under the current conditions and how can the methods be implemented for example for pharmaceutical analysis? To enlarge the range of applications, the working electrode of the electrochemical cell shall be optimized with respect to geometry and material. Materials properties, construction details and fabrication technology are the key aspects in the miniaturization part. In general, the combination of chemical research, materials properties and microfabrication shall lead to strong synergistic effects, which are required to apply the methodology in so diverse fields as (bio)analytical chemistry, proteomics, pharmaceutical analysis, and chromatography. As several industries are interested in rapidly applying the technology to be developed in their enterprises, the project is supported by the industrial partners Organon (Pharmaceuticals Oss, The Netherlands), AstraZeneca (Pharmaceuticals, Mölndal, Sweden), ESA (electrochemistry, Chelmsford, MA, U.S.A), LC Packings (nano-scale chromatography, Amsterdam, The Netherlands), Bruker Daltonics (mass spectrometry, Bremen, Germany), Ionics (mass spectrometry, Concord, ON, Canada), and Micronit (microsystem technology, Enschede, The Netherlands).