This proposal is for the purchase of a gas chromatography/mass spectrometry/data system that is capable of operating in both chemical ionization, negative ion mode (GC/NICI-MS) and electron impact ionization, positive ion mode. This instrument will be utilized by five investigators who are supported by the National Institutes of Health. Four of the projects to be supported are currently funded by the NIH and one represents a new direction for which funding is pending. The investigators and projects are as follows: (1) Alan S. Nies, M.D. (R01 HL 21308) """"""""The role of Prostaglandins in the Local Control of the Circulation"""""""". This proposal is to investigate the role of prostacyclin in mediating the effects of antihypertensive drugs. Prostacyclin productions in humans will be assessed by the urinary excretion of the major enzymatic metabolite of prostacyclin, dinor-6-keto-PGF 1alpha as measured by GC/NICI-MS. The second part of this proposal is to investigate the renal release of platelet activating factor, which will be analyzed by GC/NICI- MS. (2) Duane C. Bloedow, Ph.D. (R01 GM 29543) """"""""Hepatic Clearance of Drugs in Burn Patients"""""""". This proposal is to investigate the pharmacokinetics of model compounds, lidocaine and antipyrine, in burn patients. The analysis requires the simultaneous administration of [2H2] lidocaine orally, and an unlabelled form intravenously. The analyses of lidocaine and antipyrine and their metabolites will use mass spectrometry. (3) Keith L. Clay, Ph.D. (P01 HL 34303) """"""""Ether Lipids, Eicosanoids, and Lung Cell Pathophysiology"""""""". This proposal requires GC/NICI-MS for sensitive assays of platelet activating factor and eicosanoids at very low concentrations. (4) Joseph Gal, Ph.D. (R01 HL/GM 34789) """"""""Stereospecific Analysis of new Antiarrhythmic Agents"""""""". This proposal is to develop GC/MS methodology for the analysis of mexiletine enantiomers in serum in order to determine the stereochemical aspects of disposition when mexiletine (a racemic mixture) is administered. (5) John G. Gerber, M.D. (R01 DK 38504) """"""""Modulators of Gastric Histamine Release in vivo"""""""". This project examines the factors controlling the release of gastric histamine in the dog and requires the use of GC/NICI-MS for the assay of histamine and methylhistamine in plasma in levels of 50-100pg/ml. The available instrumentation for analyses of large numbers of samples as generated by these five projects is limited. These projects cannot proceed at an optimal rate without the instrumentation requested. The University of Colorado has a commitment to mass spectrometry and the existing Mass Spectrometry Resource Center has offered its services for training personnel and for consultation on maintenance of the requested equipment. For this proposal, the University has committed funds for renovation of space and maintenance of the requested instrument in order to ensure its optimal utilization.
