The objective of this project is the research and development of suitable bioanalytical methods to: (1) establish the structure and purity of potential anti-AIDS agents and new antiviral drugs, (2) determine physical, chemical and biochemical properties, including octanol-water partition coefficients, of these compounds and their metabolites, and (3) measure these drugs and their metabolites in biological samples to elucidate pharmacology and to determine pharmacokinetics. High- performance liquid chromatography and mass spectrometry are emphasized techniques. Sugar-fluorinated dideoxynucleosides, including 2'-F-ddA and prodrugs of 2'-F-ddI and the modified cyclodextran sulfate m-CDS71 are currently the compounds of primary interest. A high sensitivity HPLC assay involving direct fluorogenic derivatization of biological samples has been developed for the analysis of F-ddA. The role of adenosine deaminase in prodrug activation is also under investigation.
