HPLC法测定注射用唑来膦酸中3种有关物质  

Determination of three related substances in Zoledronic Acid Injection by HPLC

作　　者：王洪森 张敏 朱汉帅 刘钦伟 李辉辉 王颖 杨春 戚利强 张燕 WANG Hongsen;ZHANG Min;ZHU Hanshuai;LIU Qinwei;LI Huihui;WANG Ying;YANG Chun;QILiqiang;ZHANG Yan(Jiangsu Hengrui Pharmaceutical Co.,Ltd.,Lianyungang 222000,China;Jiangsu Original Drug Research and development Co.,Ltd.,Lianyungang 222042,China;School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,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]江苏原创药物研发有限公司,江苏连云港222042 [3]江苏海洋大学药学院,江苏连云港222005

出　　处：《药物评价研究》2023年第12期2525-2529,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《药品质量控制》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：目的建立同时测定注射用唑来膦酸中杂质B、C、D的HPLC法。方法采用Titank Phenyl-Hexyl色谱柱(250 mm×4.6 mm,5μm),以8 mg·mL^(-1)的1-辛烷磺酸钠和0.037 mg·mL^(-1)的EDTA-二钠为缓冲液,乙腈-缓冲液(4∶96)为流动相,体积流量0.8 mL·min^(-1),柱温20℃,检测波长为215 nm,进样量为10μL。结果在该色谱条件下,杂质B、C、D之间的色谱峰分离度良好;各杂质的检测限和定量限分别为126.0~454.5 ng·mL^(-1)、315.0~1515.0 ng·mL^(-1);各杂质在相应浓度范围内线性关系良好,R2在0.9993~1.0000;平均回收率在93.1%~102.5%,RSD均小于10.0%;且3批注射用唑来膦酸样品检测结果显示,杂质B、C、D的质量分数均低于0.5%。结论该方法简便、灵敏、专属性好,适用于注射用唑来膦酸中有关物质的测定。Objective An HPLC method was developed for the simultaneous determination of impurity B,impurity C and impurity D in Zoledronic Acid Injection.Methods The separation was performed on a Titank Phenyl-Hexyl column(250 mm×4.6 mm,5μm)with 8 mg·mL^(−1)sodium 1-octanesulfonate and 0.037 mg·mL^(−1)EDTA-disodium as the buffer,acetonitrile-buffer(4:96)as the mobile phase,at a flow rate of 0.8 mL·min^(−1),and the column temperature of 20℃,with a detection wavelength of 215 nm.The injection volume was 10μL.Results Under these chromatographic conditions,the peaks between impurity B,impurity C and impurity D were well separated.The limits of detection and quantification of each impurity were 126.0 to 454.5 ng·mL^(−1)and 315.0 to 1515.0 ng·mL^(−1),respectively.The linearity of each impurity in the corresponding concentration range was good,with R2 in the range of 0.9993 to 1.0000,and the average recoveries were in the range of 93.1%to 102.5%with the RSDs less than 10.0%.The test results of three batches of Zoledronic Acid Injection showed that the contents of impurities B,C and D were all lower than 0.5%.Conclusion The method is simple,sensitive and specific,and is suitable for the determination of related substances in zoledronic acid for injection.

关 键 词：注射用唑来膦酸 有关物质 高效液相色谱法 含量检测 方法学验证 

分 类 号：R932[医药卫生—生药学]