核磁共振内标法定量分析肝素钠中多硫酸软骨素

摘要

@@ 1 引言rn肝素钠是一种由葡萄糖胺,L-艾杜糖醛苷、N-乙酰葡萄糖胺和D-葡萄糖醛酸交替组成的黏多糖硫酸脂钠盐,是临床大量应用的抗凝血药.研究证明,肝素钠还具有抗炎、抗过敏、抗病毒,抗癌等多种生物学功能.2008年初,欧美各国发生了肝索钠注射液事件,致使81人死亡.随后,美国FDA应用核磁共振方法在肝素钠原料药中定性查出杂质多硫酸软骨素(OSCS),并认为OSCS是引起用药异常的杂质.肝素与OSCS均属于黏多糖硫酸脂聚合物,分子量分布都有一定宽度,且结构及性质相似,因此,常规的化学和生物检测方法很难区分[2].%The quantitative analysis of Oversulfated Chondroitin Sulfate by 1 H-NMR internal standard method has been developed in this paper. The optimum experimental conditions have been described. The linear range of the method was found to be 0. 1％-5 ％. The regression equation derived was y＝2. 7929x-0.0317(r＝0. 9994). The limit of detection was 0. 1％. The average recovery rate was shown to be 98. 1％(n＝6), and the RSD was 0.35 ％(n＝6). The results showed that 1 H-NMR can be used for the quantitative determination of contaminants in heparin.