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

IC determination of principal ions K^+ and Mg^(2+) and impurity Na^+ in the potassium aspartate and magnesium aspartate injection

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 Ion Pac^(TM)CS12A 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 m L·min^(-1),电导检测器(金工作电极、p H-Ag/Ag Cl参比电极),检测器温度30℃,柱温30℃,进样量25μL。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、1.05~16.8μg·m L^(-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 Mg^（2＋） 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 Ion Pac^（TM）CS12 A kation column（4 mm×250 mm）and a CG12 A 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 m L·min^（-1）;electrical conductivity detector（Au working electrode,p H-Ag/Ag Cl 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^（-1）6.8 μg·m L^（-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 Mg^（2＋） in sample from G factory were close to that of Panangin injection,and the contents of K^＋ and Mg^（2＋） 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 Mg^（2＋） 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.