使用HNMR和独立组件分析,同时量化粗肝素中的氏丁硫酸盐和皮质硫酸盐
René Burger1, Xuan Tung Do1, Bernd W K Diehl2
1Bonn-Rhein-Sieg University of Applied Sciences, Department of Natural Sciences, von-Liebig-Straße 20, 53359 Rheinbach, Germany.
Journal of pharmaceutical and biomedical analysis
|February 20, 2026
概括
在肝素中量化氏丁硫酸盐 (CS) 和皮质硫酸盐 (DS) 杂质对于安全至关重要. 一种新的1HNMR和独立组件分析 (ICA) 方法提供了一个更快,更简单的替代品,用于素质量控制的传统测试.
科学领域:
- 分析化学 分析化学
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 肝素是一种重要的抗凝剂,可以被氏丁硫酸盐 (CS) 和皮肤硫酸盐 (DS) 污染.
- 准确量化 CS 和 DS 在原始肝素中对于产品安全和过程监测至关重要.
- 这些糖氨基氨基甘的结构相似性和异质性带来了分析挑战.
研究的目的:
- 开发和验证一种快速准确的方法来量化肝素中CS和DS杂质.
- 为此目的,评估1H NMR与独立组件分析 (ICA) 结合的性能.
- 为了将新方法与传统的酶分析进行比较.
主要方法:
- 使用1H核磁共振 (NMR) 光谱在500 MHz和80 MHz.
- 应用独立组件分析 (ICA) 来解决CS和DS重叠的乙信号.
- 分析合成混合物和原始肝素样本.
- 与传统的酶性消化方法相比,经过验证的结果.
主要成果:
- 在两种NMR仪器中,ICA模型实现了低根平均平方误差 (RMSEs) ≤2.1% w/w.
- 500 MHz 1H NMR-ICA 方法与酶测定有很好的一致性.
- 80 MHz的基准NMR-ICA系统适用于选中等到高的杂质水平.
- 与酶方法相比,ICA-NMR的工作流显示出更高的速度和简单性.
结论:
- ICA-NMR工作流提供了一个强大的,快速的,简化的方法来量化肝素中CS和DS.
- 这种方法促进了对肝素产品的自动化现场质量控制的发展.
- 这些发现为改善肝素安全性和制造过程监测铺平了道路.
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