MASS SPECTROMETRY OF ANTITUMOR AGENTS

抗肿瘤剂的质谱分析

• 批准号: 3183414
• 负责人: KARL H SCHRAM
• 金额: $ 13.04万
• 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/3183414
• 关键词: antineoplastics; 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.

本研究的目的是应用快原子技术 轰击质谱 (FABMS) 解决涉及结构的问题 阐明合成和天然存在的抗肿瘤剂， 抗肿瘤药物的代谢物以及抗肿瘤药物之间形成的复合物 剂和寡脱氧核苷酸。 扩大业务范围的独特方法 选择可用作 FAB 基质的溶剂将是使用 可加热/可冷却探头。 FABMS 的应用也是独一无二的 完整线性和交联药物寡核苷酸的分析 加合物。 质谱结构-断裂关系将是 为那些以前未研究过或未研究过的化合物类别而开发 只是有限的程度。 天然存在的抗肿瘤物质的结构 临床上重要的抗癌药物的制剂和代谢物将 根据高分辨率质量测量暂时分配， 亚稳态研究和结构-断裂关系 在这些研究过程中发展起来。 本提案中描述的项目将合作进行 与参与设计的其他药物和药物化学家一起， 抗肿瘤药物的合成和制剂。 质量的利用 因此，光谱测定法在解决结构问题方面可能具有以下作用： 对于开发新的抗肿瘤药物或在 提高目前临床使用药物的临床疗效。 待检查化合物类别的质谱分析，例如， 一般而言，丝裂霉素C、链黑素、米托蒽醌的类似物 需要使用FAB。 电子轰击 (EI) 和化学电离 (CI) 还将用于天然产物和代谢物的鉴定 研究。 解吸化学电离 (DCI) 将作为一种 如有必要，在米托蒽醌类似物的情况下可替代 FAB。