The overall objective of the proposed research are to develop a simplified, inexpensive mass selective detector for high performance liquid chromatography (HPLC) and to demonstrate the utility of this new system for solution of significant biomedical problems. Specific objectives of Phase I include development of an efficient and reliable LC-MS interface suitable for use with smaller bore LC columns, development of simplified vacuum systems for LC-MS, and evaluation of alternative technologies for the mass analyzer and data system. Results from these studies will be applied in phase II to the development and evaluation of an inexpensive and reliable system which will allow mass spectrometry to be employed routinely as both a highly specific and nearly universal detector for HPLC. The resulting instrumentation will provide important new capabilities for the qualitative and quantitative analysis of biological substances, and will be applicable to many areas of both basic and clinical research.