优化加热电喷雾电离化参数,以最大限度地减少源源产生的杂质在分析的寡核酸治疗药物
Mollie A Glenister1, Ulrik Mistarz2, Ken Cook3
1School of Chemical, Materials and Biological Engineering, University of Sheffield, Sheffield, UK.
Rapid communications in mass spectrometry : RCM
|April 4, 2025
概括
一种新的离子对逆相液态色谱-质谱法简化了对寡核酸治疗药物的分析. 这种方法优化了源条件,以有效地表征反意义寡核酸和小干扰RNA,最大限度地减少杂质.
科学领域:
- 分析化学 分析化学
- 生物化学 生物化学
- 制药科学 制药科学
背景情况:
- 寡核酸是一种重要的治疗类.
- 它们的结构复杂性为杂质分析提出了分析挑战.
- 开发强大的分析方法对于治疗开发至关重要.
研究的目的:
- 引入一种敏感的离子对逆相液体染色体质谱法 (LC-MS) 方法.
- 分析反感性寡核酸 (ASOs) 和小干扰RNA (siRNAs).
- 描述和确定治疗性寡核酸制剂的杂质概况.
主要方法:
- 使用六胺:六二醇移动相的LC-MS分析.
- 优化电子喷射电离源条件 (碰撞能量,温度).
- 用负离子和正离子模式进行分析,以尽量减少源中的杂质和添加物.
主要成果:
- 较低的碰撞能量导致了六胺,主要是在较低的电荷状态下.
- 碰撞能量的增加减少了 adducts,但增加了气相核基损失 (源中的杂质).
- 与酸相比,开发的方法实现了更高的MS灵敏度,更高的电荷状态和有效的 adduct 移除.
结论:
- 优化的温和源条件和高pH移动相简化了寡核酸的治疗特征.
- 高分辨率精确的质谱和自动解卷增强了杂质分析.
- 这种方法简化了对寡核酸治疗药物及其杂质的表征.
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