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| Gérard Hopfgartner, University of Geneva |
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Gérard Hopfgartner studied chemistry at the University of Geneva and received his Ph.D. degree in 1991 in the field of organic geochemistry and mass spectrometry. He pursued his formation as a postdoctoral fellow at Cornell University in the domain of atmospheric pressure ionisation LC/MS/MS (1991-1992). Then he joined the DMPK department of F.Hoffmann-La Roche in Basel. During this period of almost 10 years he introduced LC-MS/MS in bioanalysis for qualitative and quantitative analysis and headed the bioanalytical section. He moved then to the University of Geneva where he is since April 2002 full Professor for Pharmaceutical Analytical Chemistry at the School of Pharmaceutical Sciences. His scientific interests are separation techniques combined with mass spectrometric detection for life sciences, high speed analysis, metabolism, collision induced fragmentation mechanisms, micro-chips and proteomics.
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Analytical Strategies for the Identification of Biomarkers in Biological Fluids
Gérard Hopfgartner, Life Sciences Mass Spectrometry, School of Pharmaceutical Sciences, EPGL University of Geneva, 20 Bd d'Yvoy, CH-1211 Geneva 4, Switzerland
In drug discovery and drug development analytical methods are mainly established to quantify a drug and to identify its metabolites circulating or accumulating in the body. Recently, more attention has been given in the analysis of biomarkers such as lipids, peptides, proteins and low molecular weight (LMW) compounds present in body fluids. The monitoring of biomarkers can serve as indicators to a biological process or to monitor the response to a therapeutic treatment. The large dynamic range of endogenous compounds and the natural variation between individuals makes the development of analytical assays for biomarkers particularly challenging.
Due to its high selectivity and sensitivity mass spectrometry (MS) has become an essential tool in the life sciences to identify and quantify exogenous and endogenous analytes in complex matrices. In combination with liquid chromatography MS is currently applied, either to perform targeted analysis, or to obtain profiles of LMW compounds. Off-line methods such as chip-based nanoelectrospray without chromatography have also shown great potential as analytical tools.
For protein analysis the situation is somehow different and 2D-gel electrophoresis combined with matrix assisted laser desorption mass spectrometry remains the technique of choice. However the preparation of 2D gels is time consuming and requires skilled users. Miniaturization and automation are therefore highly desirable.
Quantitative analysis of LMW compound is quite straightforward and internal standard can be synthesized. In the case of protein biomarkers most current differential approaches use relative and not absolute quantitation.
In the future, bioanalysis will have to face the challenge that beside the quantitation of a drug in plasma, quantitative results may also be required for dozens of selected biomarkers. Furthermore, these assays will need to be run in a regulatory environment when used to support clinical studies.
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