电感耦合等离子体质谱法测定明胶空心胶囊中元素杂质残留量

Determination of Residual Elemental Impurities in Vacant Gelatin Capsules by ICP-MS

目的建立测定明胶空心胶囊中镉、铅、砷、汞、钴、钒、镍、铬、铁、锌10种元素杂质残留量的电感耦合等离子体质谱(ICP-MS)法。方法以钪、铟、锗、铋元素为内标,载气为氦气,等离子体模式为HMI-8,载气流量为0.8 L/min,雾化气流量为0.8 L/min,辅助气流量为0.8 L/min,等离子气流量为15.0 L/min,蠕动泵转速为0.10 r/min,雾化室温度为2.0℃。结果10种元素杂质在各自质量浓度范围内与其响应值线性关系良好(r≥0.9986,n=7);加样回收率为93.26%~104.84%,RSD为0.62%~3.66%(n=6);精密度试验结果的RSD为1.23%~3.20%(n=6)。测定的36批样品中,4批样品中铅元素含量超过ICH Q3D口服限度,4批样品中铬元素含量超过控制阈值,3批样品中铁元素含量超过30μg/g。结论该方法灵敏度高,精密度和准确度均良好,能很好地控制明胶空心胶囊中的痕量元素杂质。所测36批样品有7种元素杂质的风险系数较低,铅、铬、铁3种元素杂质的风险系数较高。

Objective To establish an inductively-coupled plasma mass spectrometry(ICP-MS) method for the determination of the residual impurities of cadmium,lead,arsenic,mercury,cobalt,vanadium,nickel,chromium,iron,and zinc impurities in Vacant Gelatin Capsules.Methods With scandium,indium,germanium,and bismuth as internal standards,the carrier gas was helium,the plasma mode was HMI-8,the flow rate of carrier gas was 0.8 L/min,the flow rate of atomization gas was 0.8 L/min,the flow rate of auxiliary gas was 0.8 L/min,the flow rate of plasma gas was 15.0 L/min,the speed of peristaltic pump was0.10 r/min,and the temperature of atomization chamber was 2.0 ℃.Results There is a good linear relationship between the response values of 10 elemental impurities within their respective mass concentration ranges(r ≥ 0.998 6,n = 7).The recovery rate of the sample was in the range of 93.26%-104.84%,with RSD of 0.62%-3.66%(n = 6).The RSD of the precision test results was in the range of 1.23%-3.20%(n = 6).Among the thirty-six batches of samples,four batches had lead content exceeding the oral limit recommended by the ICH Q3D,four batches had chromium content exceeding the control threshold,and three batches had iron content exceeding 30 μg/g.Conclusion The method has high sensitivity,good precision and accuracy,which can effectively control trace element impurities in Vacant Gelatin Capsules.The risk factors of seven elemental impurities in the 36batches of samples are relatively low,while the risk factors of three elemental impurities(lead,chromium,and iron)are relatively high.