摘要
目的:依据ICH Q3D(R2)元素杂质指导原则,建立ICP-MS法检测甘露醇中1类元素杂质[砷(As)、镉(Cd)、汞(Hg)和铅(Pb)]、2A类元素杂质[钴(Co)、镍(Ni)和钒(V)]的残留量。方法:采用ICP-MS法,以氦气为载气,选取HMI-8等离子体模式,采样深度10.0 mm,射频功率1600 W,载气流量0.8 L·min^(-1),雾化气流量0.8 L·min^(-1),辅助气流量0.8 L·min^(-1),等离子气流量15.0 L·min^(-1),蠕动泵转速0.10 r·min^(-1),雾化室温度2.0℃;分析方法为内标法。结果:各元素杂质线性相关系数r均大于0.999;加样回收率在90.0%~110.0%,回收率RSD均低于5.0%;精密度RSD均低于7.0%;73批样品中7种元素杂质含量均低于ICH Q3D(R2)元素杂质指导原则中1类、2A类元素杂质的注射用每日允许暴露量(PDE)。结论:该方法灵敏度高,精密度、准确度良好,能够很好地控制甘露醇中的1类和2A类元素杂质;市售甘露醇中1类和2A类元素杂质残留风险低。
Objective:To establish an ICP-MS method to detect the residual amounts of Class 1 elemental impurities[arsenic(As),cadmium(Cd),mercury(Hg),and lead(Pb)],and Class 2A elemental impurities[cobalt(Co),nickel(Ni),and vanadium(V)]in mannitol according to ICH Q3D(R2).Methods:ICP-MS method was adopted,with helium as the carrier gas.HMI-8 plasma mode was selected,with a sampling depth of 10.0 mm,radio frequency power of 1600 W,carrier gas flow rate of 0.8 L·min^(-1),atomization gas flow rate of 0.8 L·min^(-1),auxiliary gas flow rate of 0.8 L·min^(-1),plasma gas flow rate of 15.0 r·min^(-1),peristaltic pump speed of 0.10 r·min^(-1),and atomization chamber temperature of 2.0℃.The analysis method is the internal standard method.Results:The linear correlation coefficient r of 7 elemental impurities was greater than 0.999.The recovery rates were within the range of 90.0%-110.0%.The RSD of recovery rate was less than 5.0%.The RSD of precision rate was less than 7.0%.The contents of 7 elemental impurities in 73 batches of samples were all less than permitted daily exposure(PDE)for injection set by ICH Q3D(R2).Conclusion:This method is highly sensible,reproducible,accurate and can precisely determine the Class 1 and Class 2A element impurities in mannitol;The residual risk of impurities in Class 1 and Class 2A elements in commercially available mannitol is low.
作者
郭雅娟
王彩媚
胡淑君
陈英
GUO Ya-juan;WANG Cai-mei;HU Shu-jun;CHEN Ying(Guangdong Institute for Drug Control,CFDA Key Laboratory of Quality Control and Evaluation of Pharmaceutical Excipients,Guangzhou 510663,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2023年第5期804-810,共7页
Chinese Journal of Pharmaceutical Analysis
