电感耦合等离子体质谱法测定乙磺酸尼达尼布原料药中7种杂质元素

Determination of 7 elemental impurities in nintedanib esylate drug substances by Inductively coupled plasma-mass spectrometry

建立了电感耦合等离子体质谱(ICP-MS)法测定乙磺酸尼达尼布原料药中镉、铅、砷、汞、钴、钒、镍7种元素杂质。用微波消解法进行样品处理,以ICP-MS法进行测定,射频功率为1550 W,雾化气流量为1.1 L/min,测定模式为碰撞池模式,碰撞气流量为4.8 L/min,冷却气流量为14 L/min,辅助气流量为0.8 L/min,蠕动泵转速为40 r/min。7种元素的质量浓度在线性范围内与各自的信号值线性关系良好,相关系数均不小于0.9999;检测限为0.0002~0.0060μg/g;定量限为0.001~0.019μg/g;重复性试验结果的相对标准偏差为0.7%~1.2%(n=6);各浓度点平均回收率为82.6%~119.1%(n=3)。该方法灵敏度高,准确性好,适用于乙磺酸尼达尼布原料药中元素杂质的检测。

A method for the determination of 7 elemental impurities(Cd,Pb,As,Hg,Co,V and Ni)in nintedanib esylate by inductively coupled plasma mass spectrometry(ICP-MS)was established.The samples were processed by microwave digestion and measured by ICP-MS with following condition:the radiofrequency power was 1550 W,the nebulizer flow was 1.1 L/min,measurement mode was collision cell mode with kinetic energy discrimination,the collision gas flow was 4.8 L/min,the cool gas flow was 14 L/min,the auxiliary gas flow was 0.8 L/min,the pump speed is 40 r/min.The mass concentration of the seven elements had a good linear relationship with their respective signal values in the linear range,and the correlation coefficients were not less than 0.9999.The detection limit was in the range of 0.0002-0.0060μg/g,and the quantification limit was in the range of 0.001-0.019μg/g.In repeatability,the relative standard deviation were between 0.7%and 1.2%(n=6).The average recovery rates were between 82.6%and 119.1%(n=3)for all the tested elements.The method is sensitivity and accuracy,which is suitable for the detection of trace elemental impurities in nintedanib esylate.