This proposal requests NCRR funds for purchase of a Hewlett-Packard model 5989B liquid chromatograph/electrospray mass spectrometer (lc/es ms) for the Cancer Center (CC) and the School of Medicine at Case Western Reserve University. The School of Medicine will commit supplemental funds amounting to about 25% of the purchase cost of the requested instrument. The Cancer Center will commit funds to meet the salary and contract service costs of sustaining the operation of this instrument. The group of anticipated principal users have substantial peer-reviewed research fund awards, and they include both Cancer Center members and School of Medicine faculty who are nor Cancer Center members. Any lc/es ms operational time not consumed by the principal instrument users will be offered to the School of Medicine research community. Acquisition of this instrument is an essential part of the Cancer Center's plan for development of its Clinical Pharmacology Core Facility. There is no lc/es ms instrument available at this University. The addition of this instrument to the Cancer Center's Clinical Pharmacology Core Facility will accomplish several kinds of molecular measurement needed to assure completion of PHS/NCI funded research at the Cancer Center. The lc/ms will be applied to experimental problems which require highly sensitive quantification of chemotherapeutic agents and metabolites. The CC presently has ongoing several Phase 1 and Phase 2 clinical trials which involve sustained low dose rate drug infusion. The plasma steady-state drug concentrations observed in current trials or expected in some pending studies are extremely small. In many cases those concentrations are or will be invisible to the Clinical Pharmacology Core Facility's optical chromatographic detectors. In a second broad category of research performed by Cancer Center investigators, the lc/ ms also will be used to provide good evidence of molecular structure for the identification of drug metabolites and in studies of drug action mechanism. The requested instrument is capable of accurate molecular weight measurement of proteins, peptides, oligosaccharides, and nucleotides to a limit of 150,000 a.m.u. This capability will benefit basic research within and beyond the Cancer Center.
