Speaker: Christoph Borchers Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC High-field FTICR-MS for Rapid and Comprehensive Metabolomics Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) has exceptional mass resolution, mass accuracy, precision, and sensitivity. We exploited first these properties to demonstrate the high throughput potential of FTICR-MS by identifying metabolites in aqueous human plasma extract without prior chromatography. Based on the accurate mass measurement we determined reasonable elemental compositions for approximately 250 of over 500 metabolites detected in a single 3-minute direct infusion FTICR-MS analysis of aqueous human plasma extract without up-front chromatographic separation. In these experiments we identified 100’s of these metabolites using the Kyoto Encyclopedia of Genes and Genomes database. Using internal standards we obtained excellent calibration curves (R2 >0.99) for direct quantitation of choline in plasma without chromatography. Sub-pmol detection limits were easily achieved for ~1 min analyses using 500 times less sample than previously published ESI-LC/MS analyses. In addition, we achieved sub-pmol detection limits with 500 times less sample than published ESI-LC/MS analyses, suggesting that FTICR-MS is well suited for high throughput metabolomics. In a first application of this technology we analyzed the time-dependant changes in the metabolome of mice blood serum due to the treatment with an environmental hazard (TCE). We have found several differential concentrations of metabolites which are novel and to be known demonstrating that our results are consistent with conventional methodologies. However, our FTICR-MS based metabolomic approach is less time-consuming and capable for the analysis of at least 150 samples/day. Next we will apply the FTICR-MS based metabolomics methodology to analyze more than 200 patients at the UNC hospital undergoing cardiac catheterization. In a sytems biology approach the metabolomics results obtained will be correlated to the simultaneous analysis of DNA, RNA and proteins with the clinical outcome to determine bio-molecular risk factors of cardiac diseases.