THE ANALYTICAL CHEMISTRY OF ANTI-AIDS AGENTS

本项目的目标是研究和开发适用于 分析方法：(1)建立结构和纯度 潜在的抗艾滋病药物和新型抗病毒药物，(2)确定 物理、化学和生化性质，包括辛醇-水 这些化合物及其代谢物的分配系数，以及(3) 在生物样本中测量这些药物及其代谢物以 阐明药理并测定药代动力学。高性能- 重点介绍了Mance液相色谱和质谱法 技巧。含糖的双脱氧核苷，包括 2‘-F-dd-Ara-A、2’-F-dd-Ara-I和6-取代-2‘-F-dd-嘌呤 目前主要感兴趣的化合物。高效毛细管电泳法测定水杨酸 同时测定血浆、尿液中2‘-F-Ara-Dda和2’-F-dd-Ara-I 脑脊液已经被开发、验证并应用于 测定猕猴和大鼠的血浆和脑脊液药代动力学。 2‘-F-Ara-Dda表现出增强的中枢神经系统穿透能力 尊重它在两个物种中的肌苷类似物。腺苷的作用 前药激活中的脱氨酶正在调查中。

The objective of this project is the research and development of suitable analytical 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-perfor- mance liquid chromatography and mass spectrometry are emphasized techniques. Sugar-fluorinated dideoxynucleosides, including 2'-F-dd-ara-A, 2'-F-dd-ara-I, and 6-substituted-2'-F-dd-Purines, are currently the compounds of primary interest. An HPLC method for measuring both 2'-F-ara-ddA and 2'-F-dd-ara-I in plasma, urine and cerebrospinal fluid has been developed, validated and applied to determine plasma and CSF pharmacokinetics in monkeys and rats. 2'-F-ara-ddA exhibits enhanced central nervous system penetration with respect to its inosine analogue in both species. The role of adenosine deaminase in prodrug activation is under investigation.