MASS SPECTROMETRY OF ANTITUMOR AGENTS

抗肿瘤剂的质谱分析

• 批准号: 3183412
• 负责人: KARL H SCHRAM
• 金额: $ 14.04万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-03-01 至 1989-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183412
• 关键词: chemical addition; chemical structure; crosslink; drug design /synthesis /production; drug metabolism; gas chromatography mass spectrometry; ionization; mass spectrometry; mitomycin C; mitoxantrone; oligonucleotides

The objective of this research is to apply the technique of fast atom bombardment mass spectrometry (FABMS) to problems involving the structure elucidation of synthetic and naturally occurring antitumor agents, metabolites of antitumor agents and complexes formed between antitumor agents and oligodeoxynucleotides. A unique approach to expanding the selection of solvents available for use as the FAB matrix will be the use of a heatable/coolable probe. Also unique will be the application of FABMS to the analysis of intact linear and cross-linked drug-oligonucleotide adducts. Mass spectral structure-fragmentation relationships will be developed for those compound classes not previously studied or studied to only a limited extent. The structure of naturally occurring antitumor agents and metabolites of clinically important anticancer drugs will be tentatively assigned on the basis of high resolution mass measurements, metastable on studies and the structure-fragmentation relationships developed in the course of these studies. The projects described in this proposal will be performed in collaboration with other medicinal and pharmaceutrical chemists involved in the design, synthesis and formulation of antineoplastic agents. The use of mass spectrometry in solving structural problems could, therefore, be of fundamental importance in development of new antitumoragents or in increasing the clinical efficacy of drugs currently being used clinically. Mass spectral analysis of the compound classes to be examined, e.g., analogs of mitomycin C, streptonigrin, mitoxantrone, will, in general require the use of FAB. Electron impact (EI) and chemical ionization (CI) will also be used in the natural product and metabolite identification studies. Desorption chimical ionization (DCI) will be examined as an alternative to FAB in the case of mitoxantrone analogs, if necessary.

这项研究的目的是应用快速原子的技术 轰炸质谱法（FABMS）涉及结构的问题 阐明合成和天然发生的抗肿瘤药物， 抗肿瘤剂和复合物的代谢物在抗肿瘤之间形成 试剂和寡脱氧核苷酸。 扩展的独特方法 选择可用于使用的溶剂，因为Fab矩阵将是使用 可加热/可冷探头的。 fabms的应用也将独特 分析完整的线性和交联药物 - 寡核苷酸 加合物。 质谱结构碎片关系将是 为那些以前未研究或研究的化合物类别开发 只有有限的程度。 天然发生的抗肿瘤的结构 临床上重要的抗癌药物的药物和代谢产物将是 根据高分辨率质量测量值进行暂时分配 在研究和结构碎片关系的关系上稳定 在这些研究过程中发展。 本提案中描述的项目将进行协作 与其他参与设计的药物和药物化学家， 抗肿瘤剂的合成和制剂。 质量的使用 因此，解决结构问题的光谱法可能是 在开发新的抗毒剂或中的基本意义 提高目前在临床上使用的药物的临床功效。 要检查的化合物类别的质谱分析，例如 丝霉素C的类似物，链霉菌素，mitoxantrone，通常会 需要使用晶圆厂。 电子冲击（EI）和化学电离（CI） 也将用于天然产品和代谢物鉴定 研究。 解吸嵌合电离（DCI）将被检查为 如有必要，在Mitoxantrone类似物的情况下，替代FAB。