ICP-MS同时测定注射用拉氧头孢钠中17种金属元素及其西林瓶中元素的迁移

Simultaneous Determination of 17 Metal Elements in Latamoxef Sodium for Injection and the Migration of elements from its vial by ICP-MS

关键词:  拉氧头孢钠  元素迁移  电感耦合等离子体质谱  

Key words:  latamoxef sodium  element migration  inductively coupled plasma mass spectrometry  

摘要:

目的 根据ICH Q3D最新要求，建立同时测定注射用拉氧头孢中17种金属元素及西林瓶中元素迁移的分析方法。方法 使用5%的硝酸与0.1%的金元素混合液为稀释剂，解决了测定Hg和Pb两种元素记忆效应强的问题，并且无基质干扰。以Sc、Ge、Te、Bi为内标，等离子功率1550 W，载气流量1.09 L·min-1。结果 17种元素杂质线性均良好（r2均大于0.999），定量限为0.0014~4.88 ng·mL-1，各浓度点平均回收率为90.0%~120.0%（n=3），实验RSD均小于5%（n=6）。检测结果显示来源不同企业的注射用拉氧头孢钠元素杂质含量均符合ICH要求，不同企业使用的西林瓶在元素迁移上具有差别。结论 本研究建立的方法分析速度快、干扰少、灵敏度高，可实现注射用拉氧头孢钠中元素杂质的准确定量测定。揭示了低硼硅材料生产的西林瓶会产生元素的迁移现象，提示企业应该选择更为安全稳定的注射剂包装材料。

Abstract:

OBJECTIVE According to the latest requirements of ICH Q3D, establish an analytical method for the simultaneous determination of 17 metal elements in injectable ceftriaxone and the migration of elements from vials.METHODS A mixture of 5% nitric acid and 0.1% gold element was used as the diluent, which solved the problem of strong memory effect of two elements, Hg and Pb, and there was no matrix interference. Using Sc, Ge, Te, and Bi as internal standards, the plasma power was 1550 W and the carrier gas flow rate was 1.09 L·min-1.RESULTS The linearity of the 17 elemental impurities is excellent (r2 > 0.999 for all), with quantitative limit ranges from 0.0014 to 4.88 ng·mL?1. The average recovery rates for each concentration point range from 90.0% to 120.0% (n=3), and the experimental RSD is less than 5% (n=6). The results show that the elemental impurity content in injectable ceftriaxone sodium from different manufacturers meets the ICH requirements, while there are differences in element migration from vials used by different manufacturers.CONCLUSION The method established in this study offers rapid analysis, minimal interference, and high sensitivity, enabling accurate quantification of elemental impurities in injectable ceftriaxone sodium. It reveals that vials made from low borosilicate materials may cause element migration, suggesting that manufacturers should select safer and more stable packaging materials for injectable formulations.