Applications of New Mass Spectral Techniques

新质谱技术的应用

• 批准号: 6558984
• 负责人: james a kelley
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6558984
• 关键词: 2'3' dideoxynucleoside; analytical chemistry; chemical structure; electrospray ionization mass spectrometry; fast atom bombardment mass spectrometry; gas chromatography mass spectrometry; human tissue; liquid chromatography; mass spectrometry; matrix assisted laser desorption ionization; method development; pharmacokinetics; structural biology

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. This methodology has been applied to determine the pharmacokinetics, metabolism, disposition and bioavailability of 2'-b-fluoro-2',3'-dideoxyadenosine (lodenosine, F-ddA) and its anti-HIV-active deaminated metabolite 2'-b-fluoro-2',3'-dideoxyinosine (F-ddI) during a Phase I-II clinical trial of oral F-ddA in advanced AIDS patients receiving combination antiretroviral therapy. On-line sample concentration techniques are being investigated as a prelude to interfacing capillary electrophoresis to nano-electrospray ionization mass spectrometry for the analysis of intracellular nucleotide metabolites. 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 continue. 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 is ongoing. Statistical and clustering methods are being used to select compounds representative of the structural diversity of the database for analysis. AIDS Title: Application of New Mass Spectral Methods for the Analysis of Anti-AIDS Agents

该项目的目的是开发新的质谱技术，以便为涉及的问题提供创新和/或更快的解决方案（1）化学结构确定，（2）复杂的混合物分析以及（3）生物系统中痕量成分的测量。 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.狭窄的孔，反相液相色谱已与串联质谱法结合使用，以开发一种用于表征和测量生物样品中核苷药物的通用系统。 This methodology has been applied to determine the pharmacokinetics, metabolism, disposition and bioavailability of 2'-b-fluoro-2',3'-dideoxyadenosine (lodenosine, F-ddA) and its anti-HIV-active deaminated metabolite 2'-b-fluoro-2',3'-dideoxyinosine (F-ddI) during a Phase I-II clinical trial of接受抗逆转录病毒疗法的晚期艾滋病患者的口服F-DDA。在线样品浓度技术被研究为将毛细管电泳与纳米电喷雾电离质谱法进行接口的前奏，以分析细胞内核苷酸代谢物。快速原子轰击质谱法（FAB/MS）用于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3维数据库搜索确定为HIV-1积分酶抑制剂的化合物的结构认同，质谱研究仍在继续。使用MS和NMR分析来评估NCI化学​​数据库中化合物质量的项目，以进行结构表征和确定纯度。统计和聚类方法用于选择代表数据库结构多样性的化合物进行分析。 艾滋病标题：新的质谱方法的应用用于分析反辅助代理