This application reuests funds in order to continue to serve the research interests of NIH grantees with technical expertise in the arts and practices of mass spectrometry. Core research will focus on the design, implementation, and application of time array detection (TAD). A major application of TAD will be in time-of-flight (TOF) massspectrometry to make it possible to detect and integrate all the ion current (over the complete mass range) accelerated from the ion source. This capability is expected to increase the full spectrum sensitivity of the instrument by at least an order of magnitude and increase the rate of acquiring useable spectra by an order of magnitude. Both of these features will have a profound effect on conventional GC-MS, especially with increasing emphasis on the use of capillary columns in the analysis of complex mixtures found in most biological samples. In another core project, a device for TAD will be installed on a magnetic instrument (LKB-9000) to permit a combination of magnetic field dispersion and time resolution of mass to be employed for distinguishing """"""""metastable peaks"""""""" and for performing """"""""MS/MS"""""""" analyses rapidly on a single focussing mass spectrometer. Collaborative reserach will emphasize extension of metabolic profiling methodology for organic acids in urine, plasma, and/or amniotic fluid for investigations of altered metabolism in human disease states such as diabetes and muscular dystrophy. Aberrant steriod metabolism related to xenobiotic alteration of mixed function oxidases in rats will be studied. Profiling methodology will also be used to characterize metabolic pathways in infectious parasites with the view toward developing a rational basis for corrective and prophylactic drug therapy. Requests for service and collaboration will call for analyses of physiological biochemical samples for prostaglandins, sugars, indole derivatives, etc. Many projects involving organic synthesis will continue to request exact mass measurements to validate the empirical formulas of their products. Training will continue to be an important feature in the Facility program; approximately 20 graduate students receive detailed training in mass spectrometry through research projects with the five professional investigators in the Facility program.
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