ICP-MS法测定注射用头孢美唑钠中31种元素杂质的含量  

Determination of 31 Elemental Impurities in Cefmetazole Sodium for Injection by ICP-MS

作　　者：耿悦 宋芸峰 沈杰 张锦琳 袁耀佐 GENG Yue;SONG Yunfeng;SHEN Jie;ZHANG Jinlin;YUAN Yaozuo(Jiangsu Institute of Food and Drug Administraiion,Nanjing 210019,China;NMPA Key Laboratory for Impurity Profile of Chemical Drugs,Nanjing 210019,China;Nanjing University of Traditional Chinese Medicine,Nanjing 210023,China;Shanghai Huace Aipu Medical Test Institute Co.,Ltd.,Shanghai 200040,China;Agilent Technologies Inc.,Shanghai 200080,China)

机构地区：[1]江苏省食品药品监督检验研究院,南京210019 [2]国家局化学药物杂质谱研究重点实验室,南京210019 [3]南京中医药大学,南京210023 [4]上海华测艾普医学检验所有限公司,上海200040 [5]安捷伦科技有限公司,上海200080

出　　处：《药学与临床研究》2022年第5期403-408,共6页Pharmaceutical and Clinical Research

基　　金：2021年国家药品评价性抽验资助(国药监药管[2021]1号)。

摘　　要：目的:建立电感耦合等离子体质谱(ICP-MS)法,测定注射用头孢美唑钠中的31种具有潜在风险的元素杂质:砷(As)、镉(Cd)、汞(Hg)、铅(Pb)、钴(Co)、镍(Ni)、钒(V)、金(Au)、铱(Ir)、锇(Os)、钯(Pd)、铂(Pt)、铑(Rh)、钌(Ru)、银(Ag)、硒(Se)、铊(Tl)、钡(Ba)、钼(Mo)、铬(Cr)、铜(Cu)、锂(Li)、锑(Sb)、锡(Sn)、硼(B)、铝(Al)、硅(Si)、钛(Ti)、锰(Mn)、铁(Fe),锌(Zn)的含量。方法:采用Agilent 8900 ICP-MS Triple Quad电感耦合等离子体质谱仪,运用碰撞模式消除双电荷干扰,以高基体样品进样系统模式进样,通过在线内标方式消除基质效应,样品稀释直接进样测定。结果:该方法能同时测定31种元素杂质含量,其线性关系良好(r>0.99)、重复性试验的RSD小于20%(n=6)、回收率在70%~140%(n=9),均满足USP 43<233>方法学验证碰撞模式的要求。应用该方法测定了20批来自不同生产企业的国产制剂及1批原研制剂中上述元素的含量。结论:国产及原研制剂中元素杂质含量均低于限度的30%,风险可控;所建立的方法操作简便,准确灵敏,专属性强,重复性好,可为化学药品中元素杂质控制方法提供参考。本试验对国评样品的元素杂质迁移情况开展筛查,不仅能够掌握注射用头孢美唑钠质量整体水平,并且可以为监管部门对上市后药品再评价提供技术储备和数据支持。Objective:To establish an ICP-MS method for the determination of 31 potential risk elemental impurities including As,Cd,Hg,Pb,Co,Ni,V,Au,Ir,Os,Pd,Pt,Rh,Ru,Ag,Se,Tl,Ba,Mo,Cr,Cu,Li,Sb,Sn,B,Al,Si,Ti,Mn,Fe and Zn in cefmetazole sodium for injection.Methods:Agilent8900 ICP-MS was used for determination,and a collision mode was used to eliminate double charge interferences.The contents of elemental impurities in the drugs were analyzed by high matrix injection,and the matrix effect was eliminated by online internal standard.Samples were diluted and injected directly.Results:The method simultaneously determined 31 elemental impurities.The 31 elements showed good linearities in the selected concentration ranges(r≥0.99).The relative standard deviations(RSDs)of the repeatability were less than 20.0%(n=6).The average recoveries ranged from 70%to 140%(n=9).All met the methodological validation requirements of USP 43<233>.The method was applied to the content determination of the above elements in 20 batches of domestic preparations from different manufacturers and a batch of original preparation.Conclusion:The contents of elemental impurities in cefmetazole sodium for injection are all 30%lower than their limits,and the risks are controllable.The established method is simple,accurate,sensitive,specific and reproducible.It can provide a reference for the control of elemental impurities in chemical drugs.This test carries out screening on the migration of elemental impurities in national assessment samples,which can not only grasp the overall quality level of cefmetazole sodium for injection,but also provide technical reserves and data support for the regulatory authorities to reevaluate post marketing drugs.

关 键 词：元素杂质 注射用头孢美唑钠 高基体样品进样系统模式 ICP-MS法 

分 类 号：R927.2[医药卫生—药学]