Elucidation of 10-hydroxy-7-methyl-homocamptothecin by electrospray ion trap mass spectrometry
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摘要: 目的 应用电喷雾离子阱质谱对高喜树碱类衍生物10-羟基-7-甲基-高喜树碱(TOP-01)进行质谱裂解分析,通过主要特征碎片离子研究其裂解规律。 方法 样品溶液通过仪器自带的蠕动泵进样系统直接进样分析,采用离子阱质谱的多级离子碰撞裂解方式,寻找TOP-01的特征碎片离子。 结果 TOP-01在软电离模式下,主要产生的正离子碎片分别为m/z 333、305、277、290等,负离子碎片分别为m/z 347、319、317、289、301等。 结论 TOP-01在软电离模式下、正负离子模式下质谱裂解方式存在差异,其中主要产生的正负离子碎片分别为333和347,本研究为高喜树碱及其衍生物的结构修饰及代谢研究等提供了参考依据。
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关键词:
- 高喜树碱衍生物 /
- 10-羟基-7-甲基-高喜树碱 /
- 电喷雾离子阱质谱 /
- 结构解析
Abstract: Objective To analyze the fragments of 10-hydroxy-7-methyl- homocamptothecin (TOP-01) by electrospray ion trap mass spectrometry and deduce the MS/MS fragment pathway of it. Methods Samples were directly injected into the instrument and the fragments of the samples were yielded by using multi-stage ion trap mass spectrometry. Results Fragment ions m/z 333, 305, 277, 290 were generated at the positive ion mode and m/z 347, 319, 317, 289, 301 at the negative mode for TOP-01. Conclusion Differences existed in fragmentation pathway between positive and negative ESI-MS,and the main fragmentation characteristics of TOP-01 were m/z 333 and 347 in positive and negative mode respectively. These results provided very important information for the structural modification and the drug metabolic research of homocamptothecin. -
[1] Hsiang YH,Hertzber R,Hecht S,et al.Camptothecin induced protein-linked DNA breaks vis mammalian DNA topoisomerase I [J].J Biol Chem, 1985, 260:14837. [2] Ganguly A,Das BB,Sen N'LeishMan'topoisomerase I:an ideal chimera for unraveling the role of the small subunit of unusual bisubunit topoisomerase I from Leishmania donovani[J]. Nucleic Acids Res, 2006,34(21):6286. [3] 谭慧心.拓扑异构酶 抑制剂研究进展[J].中国药理学通报,2009, 25(4): 436. [4] 杨 松,张万年.高喜树碱—极具开发价值的拓扑异构酶抑制剂[J].药学学报,2004,39(5):396. [5] 缪震元,张万年,游 亮,等.7-芳杂环高喜树碱的合成与抗肿瘤活性研究[J].中国药物化学杂志,2008, 18 (2): 105. [6] Yeh TK, Li CM, Chen CP, et al. Antitumor activities and pharmacokinetics of silatecans DB-67 and DB-91[J]. Pharmacol Res, 2010, 61: 108. [7] Lavergne O, Harnett J, Rolland A, et al. BN 80927: a novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II [J]. Bioorg Med Chem Lett, 1999, 9: 2599. [8] 李 柯,钟大放.电喷雾离子阱质谱分析喜树碱及其衍生物[J]. 质谱学报,2003, 24(增刊):37. -
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