The objective of this project is development of new mass spectral techniques in order to provide innovative and/or more rapid solutions to problems involving (1) chemical structure determination, (2) complex mixture analysis and (3) measurement of trace components in biological systems. Electrospray ionization mass spectrometry (ESI/MS), tandem mass spectrometry (MS/MS), combined liquid chromatography-mass spectrometry (LC/MS) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry are the techniques of current interest. A narrow-bore (2 mm i.d., 0.200 ml/min), reversed-phase liquid chromatography system, whose flow can be automatically diverted for on-line sample desalting, is being used in combination with tandem mass spectrometry to measure the Phase II anti-AIDS drug 2'-b-fluoro-2',3'-dideoxyadenosine (lodenosine, F-ddA), its anti-HIV-active deaminated metabolite 2'-b-fluoro-2',3'-dideoxyinosine (F-ddI) and the companion antiretroviral agent stavudine (2'-deoxythymidinene, d4T) in human plasma with high specificity and sensitivity. This methodology has been applied to determine the pharmacokinetics, metabolism and disposition of oral F-ddA during a Phase I clinical trial of this agent in AIDS patients receiving combination antiretroviral therapy. Fast atom bombardment mass spectrometry (FAB/MS) is employed to support the LMC synthetic effort through structural characterization of new compounds and synthetic intermediates. Mass spectrometric studies to confirm the structural identity of compounds identified as HIV-1 integrase inhibitors through 3-dimensional database searching are ongoing. A project to evaluate the quality of the compounds in the NCI chemical database using MS and NMR analysis for structural characterization and determination of purity has been initiated. Statistical and clustering methods are being used to select compounds representative of the the structural diversity of the database for analysis. AIDS Title: Application of New Mass Spectral Methods for the Analysis of Anti-AIDS Agents