APPLICATIONS OF NEW MASS SPECTRAL TECHNIQUES

本项目的目标是开发新的质谱学。 技术，以便提供创新和/或更快速的解决方案 涉及(1)化学结构测定，(2)络合物的问题 混合物分析和(3)生物中痕量成分的测定 系统。电喷雾电离质谱仪(ESI/MS)，串联质谱仪 光谱分析(MS/MS)和液-质联用 光谱分析(LC/MS)是当前研究的热点技术。一条狭窄的- 内径2 mm，0.200毫升/分钟，反相液相色谱 系统，其流量可以自动分流用于样品脱盐， 已经被用来开发一种利用串联质量的快速方法 一期抗艾滋病药物2‘-b-氟-2’，3‘- 二脱氧腺苷(F-Dda)及其抗HIV活性脱氨代谢产物 高血压病患者血浆中2‘-b-氟-2’，3‘-二脱氧肌苷 特异性和敏感性。这一方法正被应用于 测定口服F-Dda的药代动力学和生物利用度 该药在艾滋病患者中的初步I期临床试验。快地 原子轰击质谱仪(FAB/MS)用于支持LMCH 通过新化合物的结构表征进行合成的努力 和合成中间体。涉及离子的FAB液体基质反应 配对、还原、脱卤化和自由基阳离子/阴离子的形成 继续研究和特色化以确保可解释性 以及这些分析的可靠性。

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 employed to develop a rapid method utilizing tandem mass spectrometry for measuring the Phase I anti-AIDS drug 2'-b-fluoro-2',3'- dideoxyadenosine (F-ddA) and its anti-HIV-active deaminated metabolite 2'-b-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 LMCH 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.