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。串联电喷雾质谱(ESI/MS) 质谱仪(MS/MS)和液-质联用 光谱分析(LC/MS)是当前研究的热点技术。一个 窄孔(内径2毫米，0.200毫升/分钟)，反相液体 层析系统，其流量可自动分流用于 样品脱盐，已开发用于一般电喷雾化/质谱仪分析 生物样本。该LC/ESI/MS系统已用于开发 串联质谱仪快速测相的方法 抗艾滋病药物2‘-β-氟-2’，3‘-二脱氧腺苷(F-Dda)及其 抗HIV活性脱氨基代谢物 高血压病患者血浆中2‘-β-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。 快原子轰击质谱仪(FAB/MS)用于支持 通过新的LMC结构表征的LMC合成努力 化合物和合成中间体。FAB液体基质反应 涉及离子配对、还原、脱卤化和自由基 阳离子/阴离子的形成继续被研究和表征为 确保这些分析的可解释性和可靠性。

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 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.