离子色谱法测定门冬氨酸钾镁注射剂的钾、镁离子含量及钠离子杂质检查

目的：建立门冬氨酸钾镁注射剂钾、镁离子含量测定及钠离子杂质检查的离子色谱测定方法，评价原研工艺的D、G厂和非原研工艺的A、B、C、E、F厂的样品含量。方法：采用Dionex IonPac^TMCS12A RFIC^TM阳离子交换柱（4 mm×250 mm）和CG12A保护柱（4 mm×50 mm），淋洗液为0.02 mol·L^-1的甲烷磺酸溶液，流速1 mL·min^-1，电导检测器（金工作电极、pH-Ag/AgCl参比电极），检测器温度30 ℃，柱温30 ℃，进样量25 μL。结果：钠离子、钾离子及镁离子色谱峰与相邻色谱峰的分离良好；钠离子、钾离子、镁离子质量浓度分别在0.375~6.0、2.85~45.6、1.05~16.8 μg·mL^-1内线性关系良好，相关系数均大于0.999 9；平均回收率（n=9）分别为98.5%、101.9%、99.9%。采用原研工艺的G厂样品钾离子及镁离子含量接近原研制剂，D厂样品钾离子及镁离子含量与原研制剂偏离较大，非原研工艺的所有样品钾离子及镁离子含量均与原研制剂偏离较大，批次间含量差异大；2种工艺钠离子都有检出，非原研工艺样品中钠离子含量明显高于原研工艺。结论：经方法学验证，本方法可用于门冬氨酸钾镁注射剂的含量测定和杂质检查。

Objective: To establish the method for determination of the contents of K⁺ and Mg²⁺ and impurity Na⁺ in potassium aspartate and magnesium aspartate injection by ion chromatography,and to evaluate the sample contents of the original process in D and G factories,and the non-original process of A,B,C,E,F factories. Methods: The chromatographic separation was performed on a Dionex IonPac^TMCS12A kation column(4 mm×250 mm)and a CG12A guard column(4 mm×50 mm). The mobile phase was 0.02 mol·L^-1 methane sulfonic acid solution; the flow rate was 1.0 mL·min^-1;electrical conductivity detector(Au working electrode,pH-Ag/AgCl reference electrode)was adopted;the temperature of electrical conductivity detector and column were both 30 ℃;the injection volume was 25 μL. Results: The chromatographic peaks of Na⁺,K⁺ and Mg²⁺ ions were well separated from the adjacent peaks. Na⁺,K⁺,Mg²⁺ had good linear relationship in the ranges of 0.375-6.0,2.85-45.6,and 1.05-16.8 μg·mL^-1,respectively. All of the correlation coefficients were 0.999 9. The average recoveries were 98.5%,101.9% and 99.9%. D and G factories had the same production technique with Panangin injection. The contents of K⁺ and Mg²⁺ in sample from G factory were close to that of Panangin injection,and the contents of K⁺ and Mg²⁺ in sample from D factory deviated from that of Panangin injection;production techniques of A,B,C,E and F factories were the same,which were different from Panangin injection. The contents of K⁺ and Mg²⁺ in sample from these five factories deviated from that of Panangin injection. Na⁺ was detected in all samples covering all seven factories,and there were significantly more Na⁺ in A,B,C,E and F factories. Conclusion: The established method is proved by methodology validation that it can be used for the content determination and impurity detection of potassium aspartate and magnesium aspartate injection.