HPLC法测定唑来膦酸原料药及粉针剂中主成分唑来膦酸  

Determination of zoledronic acid as main ingredient in zoledronic acid API and powder injection by HPLC

作　　者：刘钦伟 张敏[3] 朱汉帅 闫占宽 张燕 李军毅 王维平 王洪森 LIU Qinwei;ZHANG Min;ZHU Hanshuai;YAN Zhankuan;ZHANG Yan;LI Junyi;WANG Weiping;WANG Hongsen(Jiangsu Hengrui Pharmaceutical Co.,Ltd.,Lianyungang 222000,China;Jiangsu Original Drug R&D Co.,Ltd.,Lianyungang 222000,China;School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China)

机构地区：[1]江苏原创药物研发有限公司,江苏连云港222000 [2]江苏恒瑞医药股份有限公司,江苏连云港222000 [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2515-2519,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：目的建立测定唑来膦酸原料药及粉针剂中主成分唑来膦酸含量的HPLC法。方法采用Kromasil100-5-C_(18)(250 mm×4.6 mm,5μm)色谱柱,制备0.2%的三乙胺溶液、用磷酸调pH至4.0作为缓冲液,乙腈-缓冲液(4∶96)为流动相,体积流量为0.8 mL·min^(-1),检测波长为215 nm,柱温为25℃,进样量10μL。结果唑来膦酸与相邻峰的分离效果良好,分离度为3.9,主成分唑来膦酸在100.2~1002.0μg·mL^(-1)线性关系良好,R2为0.9986,检测限和定量限分别为75.2、250.5 ng·mL^(-1),回收率在105.2%~111.4%,重复性试验、中间精密度试验、稳定性、耐用性符合要求。3批原料药和粉针剂的检测结果显示,唑来膦酸的质量分数均≥95.0%。结论经方法学验证,所建立方法灵敏、高效、专属性强、准确度高,可作为测定唑来膦酸原料药及粉针剂主成分唑来膦酸含量的方法。Objective An HPLC method was developed for the simultaneous determination of zoledronic acid in API and powder formulations.Method A Kromasil 100-5-C_(18)(250 mm×4.6 mm,5μm)column was used for the quantitative analysis of the main components.The mobile phase was acetonitrile-triethylamine solution(4:96),pH adjusted to 4.0 with phosphoric acid,at a flow rate of 0.8 mL·min^(−1),detection wavelength of 215 nm,column temperature of 25℃and injection volume of 10μL.Results The separation of zoledronic acid from the surrounding peaks was good,the degree of separation is 3.9.The linear range of the principal component zoledronic acid was good from 100.2 to 1002.0μg·mL^(−1)with the correlation coefficients R2 greater than 0.9986.The limits of detection and limits of quantification of the principal component zoledronic acid were 75.2 and 250.5 ng·mL^(−1),respectively.The recoveries of the main ingredient zoledronic acid were in the range of 105.1%—111.4%and repeatability test,intermediate precision test,stability and durability meet the requirements.The results of the three batches of API and powder injection showed that the content of the main ingredient zoledronic acid was higher than 95%.Conclusion The results of the methodological validation showed that the established method was proved to be sensitive,efficient,specific and accurate,and can be used as a method for determining the content of zoledronic acid API and powder injection.

关 键 词：唑来膦酸 高效液相色谱法 含量检测 原料药 粉针剂 

分 类 号：R932[医药卫生—生药学]