电感耦合等离子体质谱法测定止咳片中重金属含量及安全评估

Determination of heavy metals in zhike tablets by inductively coupled plasma mass spectrometry and its safety assessment

目的测定中成药止咳片中重金属元素的含量,评估其安全性。方法建立电感耦合等离子体质谱法(Inductively Coupled Plasma Mass Spectrometry,ICP-MS),测定止咳片中银、砷、钡、镉、铬、铜、铁、镍、铅、锑、锡、锌元素的含量,依据各元素含量和该药品的最大日服用量,计算日暴露量,与《中国药典》元素杂质每日允许暴露量(Permitted Daily Exposure,PDE)比较,评价其安全性。结果ICP-MS方法学参数能满足分析要求,各元素标准曲线线性相关系数大于0.9995,检出限和定量限低,精密度高,准确度好,标准物质测定值与标准值一致,样品低、中、高浓度加标回收率在80%~110%之间。样品中锡、锑含量小于检出限,银小于定量限,铁最高,超过200μg/g,其次为钡,在10μg/g左右,铜、锌含量在1.5~2.8μg/g之间,镉、砷、铬、铅含量小于1μg/g。服用该药品,各元素日暴露量与PDE值比较,占比最高者为铅,大于91%,其他元素则小于10%。结论ICP-MS方法测定止咳片中十二种重金属元素,方法可靠,结果准确。所测重金属元素每日最大暴露量都均在允许范围之内,但铅存在一定的风险。

Objective To determine the content of heavy metal elements in Zhike tablet and evaluate its safety.Methods An ICP-MS method was established for the determination of Ag,As,Ba,Cd,Cr,Cu,Fe,Ni,Pb,Sb,Sn and Zn in Zhike tablets.According to the content of each element and the maximum daily dosage of the drug,the daily exposure amount was calculated and compared with the Permitted Daily Exposure(PDE)amount of element impurities in Chinese Pharmacopoeia.The tablet’s safety of heavy metals was evaluated.Results The parameters of ICP-MS method can meet the requirements of analysis,the linear correlation coefficient of standard curve of each element is greater than 0.9995,the detection limit(LOD)and the quantitative limit(LOQ)are low,the precision is high,and the accuracy is well.The test results of certified reference materials(CRM)are consistent with the reference values,the recoveries of the samples spiked by low,medium and high concentration were between 80%and 110%.The contents of tin and antimony in the samples were less than the LOD,silver was less than LOQ and over LOD,iron was the highest,over 200μg/g,barium was next,about 10μg/g,copper and zinc were between 1.5-2.8μg/g,the contents of Cd,As,Cr and Pb were less than 1μg/g.When compared with PDE value,lead accounted for 91%and other elements less than 10%of daily exposure.Conclusion The ICP-MS method for the determination of twelve heavy metal elements in Zhike tablets is reliable and accurate.The maximum daily exposure of each heavy metal element was within the permitted range,but there was a certain risk in lead.