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1 600 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 1 600 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.
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