APPLICATIONS OF NEW MASS SPECTRAL TECHNIQUES

新质谱技术的应用

• 批准号: 2463715
• 负责人: J 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/2463715
• 关键词: 2'3' dideoxynucleoside; analytical chemistry; analytical method; chemical structure; electrospray ionization mass spectrometry; fast atom bombardment mass spectrometry; gas chromatography mass spectrometry; liquid chromatography; mass spectrometry; method development; pharmacokinetics

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) and combined liquid chromatography-mass spectrometry (LC/MS) 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 sample desalting, has been developed for general ESI/MS analysis of biological samples. This LC/ESI/MS system has been used to develop a rapid method utilizing tandem mass spectrometry for measuring the Phase I anti-AIDS drug 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA) and its anti-HIV-active deaminated metabolite 2'-beta-fluoro-2',3'-dideoxyinosine (F-ddI) in human plasma with high specificity and sensitivity. This methodology is being applied to determine the pharmacokinetics and bioavailability of oral F-ddA during the initial Phase I clinical trial of this agent in AIDS patients. Fast atom bombardment mass spectrometry (FAB/MS) is used to support the LMC synthetic effort through structural characterization of new compounds and synthetic intermediates. FAB liquid matrix reactions involving ion pairing, reduction, dehalogenation and radical cation/anion formation continue to be studied and characterized to ensure the interpretability and reliability of these analyses.

该项目的目的是开发新的质谱 为了提供创新和/或更快的解决方案的技术 涉及（1）化学结构确定的问题，（2）复合物 混合物分析和（3）生物学中痕量成分的测量 系统。 电喷雾电离质谱法（ESI/MS），串联 质谱法（MS/MS）和液相色谱 - 质量质量 光谱法（LC/MS）是当前感兴趣的技术。 一个 窄孔（2 mM I.D.，0.200 mL/min），相反的液体 色谱系统，其流动可以自动转移 样品脱盐，已开发用于一般的ESI/MS分析 生物样品。 该LC/ESI/MS系统已用于开发 利用串联质谱的快速方法来测量相位 i抗艾滋病药物2'-beta-fluoro-2'，3'-二氧化核苷（F-DDA）及其 抗HIV活性脱氨酸代谢产物 2'-beta-fluoro-2'，3'-二氧氨基氨酸（F-DDI） 特异性和灵敏度。 该方法正在应用于 确定口服F-DDA的药代动力学和生物利用度 该药物在AIDS患者中的初始I期临床试验。 快速原子轰击质谱法（FAB/MS）用于支持 LMC合成努力通过新的结构表征 化合物和合成中间体。 FAB液体基质反应 涉及离子配对，还原，去足气和自由基 继续研究阳离子/阴离子的形成并将其描述为 确保这些分析的解释性和可靠性。