APPLICATIONS OF NEW MASS SPECTRAL TECHNIQUES

该项目的目标是开发新的质谱学技术，以便为涉及(1)化学结构确定、(2)复杂混合物分析和(3)生物系统中痕量组分测量的问题提供创新和/或更快速的解决方案。电喷雾电离质谱仪(ESI/MS)、串联质谱仪(MS/MS)、液-质联用(LC/MS)和基质辅助激光解吸电离(MALDI)是目前研究的热点。利用窄口径(2 mm内径，0.200毫升/分钟)反相色谱系统，可自动分流在线样品脱盐，建立了一种利用串联质谱仪快速测定人血浆中II期抗艾滋病药物2-b-氟-2，3-二脱氧腺苷(lodenosine，F-Dda)及其抗艾滋病毒活性脱氨代谢物2-b-氟-2，3-二脱氧肌苷(F-DDI)和伴随的抗逆转录病毒药物司他夫定(2-脱氧胸腺苷，d4T)的方法。在接受联合抗逆转录病毒治疗的艾滋病患者的第一阶段临床试验中，这种方法学正被应用于确定口服F-Dda的药代动力学、代谢和处置。快原子轰击质谱仪(FAB/MS)用于通过对新化合物和合成中间体的结构表征来支持LMC的合成工作。通过三维数据库搜索确认被确认为HIV-1整合酶抑制剂的化合物的结构同一性的质谱学研究正在进行中。涉及离子配对、还原、脱卤化和自由基阳离子/阴离子形成的FAB液体基质反应仍在继续研究和表征，以确保这些分析的可解释性和可靠性。艾滋病标题：新的质谱学方法在抗艾滋病药物分析中的应用-电喷雾电离、液相-质谱学、质谱学、药代动力学、串联质谱学、2‘-β-氟-2’，3‘-二脱氧腺苷、-人体组织、液体、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.