在分析,净化和储存过程中透露脱和异酸盐的形成,通过双重质谱法进行净化和储存
V Erckes1, L Chamera Rendueles1, A Misiek1
1Laboratory of Pharmaceutical Analytics, ETH Zurich, Institute of Pharmaceutical Sciences Zurich Switzerland christian.steuer@pharma.ethz.ch.
RSC medicinal chemistry
|January 16, 2026
概括
脱化和异酸盐的形成是常见的,但很难检测到. 使用CID和ETD的双重质谱 (MS/MS) 有效地监测这些修饰,确保药物发现期间的完整性.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 药物发现 药物发现 药物发现
背景情况:
- 和模仿剂在药物发现中至关重要.
- 脱化和异酸盐的形成是常见的,具有挑战性的基修饰.
- 传统方法很难检测出这些微妙的结构变化.
研究的目的:
- 评估双重质谱法 (MS/MS) 用于检测脱胺和异酸盐形成.
- 为了进行修饰分析,比较碰撞诱导解离 (CID) 和电子转移解离 (ETD).
- 研究各种实验室条件对稳定性的影响.
主要方法:
- 使用CID和ETD的双重质谱 (MS/MS) 测量.
- 在阿斯巴拉金,谷氨酸和C端氨基酸中脱化和异酸盐形成的分析.
- 在酸性,性和中性条件下的稳定性的系统评估.
主要成果:
- 没有染色学,CID和ETD差异化改性.
- 通过ETD,可以半定量检测除化和异酸盐的形成.
- 在基本条件下形成的异酸盐;在酸性条件下发生的脱化,特别是用三酸 (TFA).
- 特别是C端胺对脱化特别容易发生.
结论:
- MS/MS,特别是ETD,是检测修饰的强大工具.
- 常规的实验室条件可以很容易诱导降解.
- 在合成和净化过程中,仔细的分析监测是必不可少的,以确保结构完整.
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