离子色谱法测定唑来膦酸原料药及其粉针剂中有关物质磷酸盐和亚磷酸盐  

Determination of related substances phosphate and phosphite in zoledronic acid API and its powder-injection by ion chromatography

作　　者：张燕 王维平 闫占宽 朱汉帅 张敏 刘钦伟 杨春 王洪森 ZHANG Yan;WANG Weiping;YAN Zhankuan;ZHU Hanshuai;ZHANG Min;LIU Qinwei;YANGChun;WANG Hongsen(Jiangsu Hengrui Pharmaceutical Co.,Ltd.,Lianyungang 222000,China;School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China;Jiangsu Original Drug Research and development Co.,Ltd.,Lianyungang 222042,China)

机构地区：[1]江苏恒瑞医药股份有限公司,江苏连云港222000 [2]江苏海洋大学药学院,江苏连云港222005 [3]江苏原创药物研发有限公司,江苏连云港222042

出　　处：《药物评价研究》2023年第12期2530-2534,共5页Drug Evaluation Research

基　　金：江苏省产教融合一流课程《药物分析》建设项目;江苏海洋大学专业学位研究生课程案例库建设项目(YJSZY202102);江苏海洋大学2023年一流课程《药物仪器分析》建设项目;连云港市政策引导产学研项目(CYX2202)。

摘　　要：目的建立一种同时测定唑来膦酸原料药及其粉针剂中的磷酸盐和亚磷酸盐的离子色谱方法。方法采用Dionex^(TM)IonPac^(TM)AS18Analytical(250 mm×4 mm)色谱柱,Dionex^(TM)IonPac^(TM)AG18Analytical(50 mm×4 mm)为保护柱,以碳酸钠和碳酸氢钠水溶液为淋洗液进行等度洗脱,体积流量为1.0 mL·min^(-1),采用抑制型电导检测器检测。结果亚磷酸根和磷酸根与相邻峰的分离效果良好,分离度均大于1.5。亚磷酸根和磷酸根分别在2.075~20.750μg·mL^(-1)和2.000~20.000μg·mL^(-1)范围内线性关系良好,相关系数均大于0.9989;原料药中亚磷酸根和磷酸根的回收率分别在94.7%~108.0%和98.4%~106.3%,回收率RSD分别为3.6%和2.3%;粉针剂中亚磷酸根和磷酸根回收率分别在93.9%~100.4%和98.2%~104.4%,回收率RSD分别为2.5%和1.9%;重复性、精密度、耐用性、溶液稳定性均符合要求。3批原料药及粉针剂中均未检出亚磷酸根和磷酸根杂质。结论该方法准确、灵敏、操作简单,适用于唑来膦酸及其粉针剂中磷酸盐和亚磷酸盐杂质的质控研究。Objective A method for simultaneous determination of phosphate and phosphite in zoledronic acid and its powderinjection by ion chromatography was developed.Methods A Dionex^(TM)IonPac^(TM)AS18Analytical(250 mm×4 mm)column and a Dionex^(TM)IonPac^(TM)AG18Analytical(50 mm×4 mm)guard column were used for isocratic elution with aqueous sodium carbonate and sodium bicarbonate as the eluent.The flow rate was 1.0 mL·min^(−1),and the detection was performed with a suppression type conductivity detector.Results The separation of phosphite and phosphate from the surrounding peaks was good,and the separation was greater than 1.5.The linear ranges of phosphite and phosphate were 2.075 to 20.750μg·mL^(−1)and 2.000 to 20.000μg·mL^(−1),respectively,with the correlation coefficients R2 greater than 0.9989.The recovery rates of phosphates and phosphates in the raw materials are 94.7%to 108.0%and 98.4%to 106.3%,respectively,with RSDs of 3.6%and 2.3%.The recovery rates of phosphates and phosphates in the powder injection were 93.9%to 100.4%and 98.2%to 104.4%,respectively,with RSDs of 2.5%and 1.9%;The repeatability,precision,durability,and solution stability all meet the requirements.No phosphite and phosphate impurity were detected in the 3 batches of raw materials and powder injection.Conclusion The method is accurate,sensitive,simple to operate,and is suitable for the quality control of phosphate and phosphite impurities in zoledronic acid and its powder injection.

关 键 词：唑来膦酸 有关物质 离子色谱法 磷酸盐 亚磷酸盐 

分 类 号：R932[医药卫生—生药学]