Applications of New Mass Spectral Techniques

该项目的目标是开发新的质谱技术，以提供创新和/或更快速的解决方案，解决涉及（1）化学结构测定，（2）复杂混合物分析和（3）生物系统中痕量成分的测量。电喷雾离子化质谱（ESI/MS）、串联质谱（MS/MS）、液相色谱-质谱联用（LC/MS）、毛细管电泳-质谱联用（CE/MS）和基质辅助激光解吸电离（MALDI）质谱是当前感兴趣的技术。窄口径，反相液相色谱法已与串联质谱法相结合，以开发一个通用的系统，用于表征和测量生物样品中的核苷类药物。在线样品浓缩技术正在研究作为一个前奏接口CE纳米电喷雾电离质谱分析细胞内的核苷酸代谢物。作为一种将CE与高分辨率MALDI/MS和源后衰变裂解分析相结合的离线方法，也正在研究同位素级CE。采用快速原子轰击质谱法（FAB/MS）通过新化合物和合成中间体的结构表征来支持LMC合成工作。通过三维数据库检索确认被鉴定为HIV-1整合酶抑制剂的化合物的结构特性的研究仍在继续。利用质谱和核磁共振分析来确定结构特征和确定纯度，评价国家化学研究所化学数据库中化合物质量的项目已接近完成。已使用统计和聚类方法来选择代表该化学上可访问的超过250，000个结构的小分子数据库的结构多样性的化合物用于分析。由于检测的化合物中有31%被评定为不可接受（没有光谱证据表明样品中存在超过50%的所需化合物或污染物），因此在使用该数据库中的化合物时必须小心。 AIDS题目：新型质谱方法在抗艾滋病药物分析中的应用

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), combined capillary electrophoresis-mass spectrometry (CE/MS) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry are the techniques of current interest. Narrow-bore, reversed-phase liquid chromatography has been combined with tandem mass spectrometry to develop a general purpose system for characterizing and measuring nucleoside-based drugs in biological samples. On-line sample concentration techniques are being investigated as a prelude to interfacing CE to nano-electrospray ionization mass spectrometry for the analysis of intracellular nucleotide metabolites. Preparative-scale CE is also being investigated as an off-line method for combining CE with high resolution MALDI/MS and post-source decay fragmentation analysis. Fast atom bombardment mass spectrometry (FAB/MS) is employed to support the LMC synthetic effort through structural characterization of new compounds and synthetic intermediates. Studies to confirm the structural identity of compounds identified as HIV-1 integrase inhibitors through 3-dimensional database searching continue. A project to evaluate the quality of compounds in the NCI chemical database using MS and NMR analysis for structural characterization and determination of purity is nearing completion. Statistical and clustering methods have been used to select compounds representative of the structural diversity of this publically accessible, small molecule database of over 250,000 structures for analysis. Since 31% of the compounds examined have been rated as unacceptable (no spectral evidence for the presence of the desired compound or contaminants exceed 50% of the sample), care must be exercised in using compounds from this database. AIDS Title: Application of New Mass Spectral Methods for the Analysis of Anti-AIDS Agents