目的 建立测定蒙脱石散中7种重金属元素的方法。方法 采用振荡水浴模拟体内代谢过程，在pH 1.2盐酸条件下处理样品6 h，用电感耦合等离子体质谱仪（ICP-MS）测定蒙脱石散中7种重金属元素Pb、Cd、Hg、Co、V、Ni、As，并用此方法测定3批自制制剂、3批原研制剂及3批蒙脱石原料药中Pb、Cd、Hg、Co、V、Ni、As的质量分数，来评估其安全性。结果 蒙脱石散中Pb、Cd、Hg、Co、V、Ni、As 7种重金属元素分别在0~30、0~1、0~6、0~10、0~20、0~40、0~4 ng/mL线性关系良好；精密度RSD分别为4.91%、5.39%、10.00%、4.78%、5.93%、4.67%、6.91%；稳定性RSD分别为5.64%、5.12%、10.94%、3.68%、4.97%、4.31%、7.06%；重复性RSD分别为4.22%、4.53%、11.22%、4.45%、6.23%、4.36%、5.64%；其平均回收率分别为102.0%、100.8%、100.5%、100.8%、101.8%、103.7%、107.6%，RSD值分别为2.06%、2.02%、2.23%、1.37%、2.34%、1.60%、7.38%；检测限为0.002~0.084 ng/mL，定量限为0.006~0.252 ng/mL。3批自制制剂、3批原研制剂及3批蒙脱石原料药中7种重金属元素平均质量分数分别为Pb 3.225、2.877、3.265 ng/g；Cd 0.062、0.071、0.070 ng/g；Hg均未检出；Co 0.192、0.093、0.213 ng/g；V 0.329、0.578、0.584 ng/g；Ni 0.363、0.124、0.296 ng/g；As 0.247、0.312、0.273 ng/g。其中，Pb、As符合《欧洲药典》中蒙脱石的标准限度，其余5种元素的量符合ICH Q3D中的PDE值（最大日服用量为10 g的药品中每个元素允许的最大数转换值），并得出制剂中7种重金属元素来源于原料药蒙脱石。结论 此方法准确、可靠，可应用于蒙脱石散中7种重金属元素的定量检查，为蒙脱石散质量控制提供一种有效的技术手段。

Objective A method was established to determine the content of seven heavy metals in Montmorillonite Powder (MP). Methods The metabolic process of the body was simulated by oscillating water bath, the sample was treated under the condition of pH 1.2 hydrochloric acid for 6 h, the seven heavy metals Pb, Cd, Hg, Co, V, Ni, and As in MP were determined by ICP-MS, and the content of Pb, Cd, Hg, Co, V, Ni, As in three batches of homemade preparations, three batches of original development agent and three batches of raw materials were determined by this method to evaluate their safety. Results The content of seven heavy metals Pb, Cd, Hg, Co, V, Ni, and As in MP had good linear relationship in the ranges of 0-30, 0-1, 0-6, 0-10, 0-20, 0-40, and 0-4 ng/mL, respectively; The RSD of precision results were 4.91%, 5.39%, 10.00%, 4.78%, 5.93%, 4.67%, and 6.91%, respectively; The RSD of stability results were 5.64%, 5.12%, 10.94%, 3.68%, 4.97%, 4.31%, and 7.06%, respectively; The RSD of repetitive results were 4.22%, 4.53%, 11.22%, 4.45%, 6.23%, 4.36%, and 5.64%, respectively; The average recoveries were 102.0%, 100.8%, 100.5%, 100.8%, 101.8%, 103.7%, and 107.6%, and the RSD were 2.06%, 2.02%, 2.23%, 1.37%, 2.34%, 1.6% and 7.38%, respectively; The detection limits were 0.002-0.084 ng/mL, and the quantitative limits were 0.006-0.252 ng/mL. The average content of seven kinds of heavy metal elements in three batches of homemade preparations, three batches of original development agent and three batches of raw materials were 3.225, 2.877, 3.265; 0.062, 0.071, 0.070 ng/g; not detected, not detected, not detected; 0.192, 0.093, 0.213 ng/g; 0.329, 0.578, 0.584 ng/g; 0.363, 0.124, 0.296 ng/g; 0.247, 0.312, 0.273 ng/g. The content of Pb and As were in accordance with the standard limit of montmorillonite in the European Pharmacopoeia, and the content of the remaining five elements were in accordance with the PDE (maximum number was allowed for each element in a drug with a maximum daily dose of 10 g) value in ICH Q3D, and it was concluded that seven kinds of heavy metal elements in the preparation were derived from the raw drug montmorillonite. Conclusion This method is accurate and reliable, which can be applied to the quantitative examination of seven heavy metals in MP, and provides an effective technical means for the quality control of MP.

R286.02