APPLICATIONS OF NEW MASS SPECTRAL TECHNIQUES

该项目的目标是开发新的质谱技术，以便为涉及(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测量的问题提供创新和/或更快速的解决方案。电喷雾电离质谱法（ESI/MS）、串联质谱法（MS/MS）、液相色谱-质谱联用法（LC/MS）和基质辅助激光解吸电离质谱法（MALDI）是目前研究的热点技术。采用一种可自动转移流量用于在线样品脱盐的小孔径反相液相色谱系统，开发了一种串联质谱快速测定II期抗艾滋病药物2-b-氟-2,3-二脱氧腺苷（lodenosine, F-ddA）、其抗hiv活性脱胺代谢物2-b-氟-2,3-二脱氧腺苷（F-ddI）及其伴生抗逆转录病毒药物他夫定（2-脱氧胸苷）的方法。d4T)在人血浆中具有高特异性和敏感性。在接受抗逆转录病毒联合治疗的艾滋病患者的I期临床试验中，该方法被用于确定口服f - da的药代动力学、代谢和处置。快速原子轰击质谱（FAB/MS）通过对新化合物和合成中间体的结构表征来支持LMC合成工作。质谱研究正在进行中，通过三维数据库搜索来确认被鉴定为HIV-1整合酶抑制剂的化合物的结构特征。FAB液体基质反应涉及离子配对、还原、脱卤和自由基正阴离子形成，继续进行研究和表征，以确保这些分析的可解释性和可靠性。题目：新型质谱方法在抗艾滋病药物分析中的应用——电喷雾电离、液相色谱-质谱、质谱、药代动力学、串联质谱、2′- β -氟-2′、3′-二脱氧腺苷、人体组织、体液、细胞等。

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) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry 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 on- line sample desalting, is being employed to develop a rapid method utilizing tandem mass spectrometry for measuring the Phase II anti-AIDS drug 2-b-fluoro-2,3-dideoxyadenosine (lodenosine, F-ddA), its anti-HIV- active deaminated metabolite 2-b-fluoro-2,3-dideoxyinosine (F-ddI) and the companion antiretroviral agent stavudine (2-deoxythymidinene, d4T) in human plasma with high specificity and sensitivity. This methodology is being applied to determine the pharmacokinetics, metabolism and disposition of oral F-ddA during a Phase I clinical trial of this agent in AIDS patients receiving combination antiretroviral therapy. Fast atom bombardment mass spectrometry (FAB/MS) is used 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 are ongoing. 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.AIDS Title: Application of New Mass Spectral Methods for the Analysis of Anti-AIDS Agents - electrospray ionization, liquid chromatography - mass spectrometry, mass spectrometry, pharmacokinetics, tandem mass spectrometry, 2'-beta- fluoro-2',3'-dideoxyadenosine, - Human Tissues, Fluids, Cells, etc.