This request is for funds to purchase mass selective detectors for the Center for Clinical Pharmacology at the University of Pittsburgh. Specifically, the Hewlett-Packard 5973 will provide us with negative ion chemical ionization capabilities and the HP1100 LC/MSD will provide a LC-MS instrument for use in routine quantitation. This instrumentation will be used in three major project areas: steroid metabolism, drug metabolism/clinical trials, and drug discovery. For the steroid metabolism project, the increased sensitivity of NICI will allow the quantitation of unconjugated steroids and their metabolites in archived samples. The availability of an LC/MS for routine use will allow us to directly quantitate conjugated steroids and their metabolites. The Center for Clinical Pharmacology has an extensive drug metabolism program with projects extending from in vitro metabolism to clinical trials. The score and quality of our drug metabolism and pharmacokinetic studies will be greatly enhanced by expanded mass spectral capabilities. Drug discovery projects include the design and synthesis of microtubule stabilizing and destabilizing agents, and the design and synthesis of adenosine deaminase inhibitors. The versatility, ease of use, and low maintenance of this instrumentation will result in increased analytical capability in many areas of biological research.
