目的 采用电感耦合等离子体质谱（ICP-MS）法测定甲磺酸卡莫司他原料药中镉（Cd）、铅（Pb）、砷（As）、汞（Hg）、钴（Co）、矾（V）、镍（Ni）、铬（Cr）8种无机元素的含量。方法 用微波消解进行样品前处理；以⁷³Ge、¹¹⁵In、²⁰⁹Bi为内标，采用ICP-MS进行测定，射频功率1 550 W，雾化气流量1.1 L·min^-1，雾化室温度2.7℃，测量模式为碰撞池模式（KED），碰撞气体积流量4.3 mL·min^-1，冷却气体积流量14.0 L·min^-1，辅助气体积流量0.8 L·min^-1，泵速40 r·min^-1。结果 8种元素标准曲线的相关系数均大于0.990；加样回收率在88.9%~124.7%（n=3）；重复性试验RSD为0.9%~2.3%（n=6）；中间精密度试验RSD为1.0%~13.8%（n=12），均满足USP<233>方法学验证的要求。样品检测的结果远小于国际人用药物注册技术协调会议《元素杂质指导原则Q3D》（ICH Q3D）中各无机元素的每日允许暴露量（PDE）。结论 建立的ICP-MS法样品用量少，分析速度快、灵敏度高，可用于甲磺酸卡莫司他原料药中无机元素的含量测定。

Objective To establish an inductively coupled plasma mass spectrometry (ICP-MS) method for determination cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg), cobalt (Co), vanadium (V), nickel (Ni), chromium (Cr) of eight inorganic elements in drug substances of Camostat Mesilate. Methods Microwave digestion was adopt for sample pretreatment. ⁷³Ge, ¹¹⁵In, ²⁰⁹Bi were chose as internal standard elements, and an inductively coupled plasma mass spectrometry method was established with following conditions: the radiofrequency (RF) power was 1 550 W, the nebulizer flow was 1.1 L·min^-1 the nebulizer temperature was 2.7 ℃, measurement mode was collision cell mode with kinetic energy discrimination (KED), the collision gas flow was 4.3 mL·min^-1, the cool gas flow was 14.0 L·min^-1, the auxiliary flow was 0.8 L·min^-1, the pump speed is 40 r·min^-1. Results Regression coefficients of standard curve of those eight element impurities were beyond 0.990. The average recovery rates were between 88.9%—124.7% (n = 3). In repeatability, the RSD were between 0.9%—2.3% (n = 6). In intermediate precision, the RSD were between 1.0%—13.8% (n = 12). All meet the requirements of USP<233> methodological verification. The determined values were well below Permitted Daily Exposure (PDE) of elemental impurities in International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH Q3D). Conclusion Methods established in this study has a fast analysis speed, a high sensitivity, and it only requires a small amount of sample which can support the determination of eight inorganic elements in drug substances of Camostat Mesilate.

R917

中国医学科学院医学与健康科技创新工程项目资助（2019-I2M-5-020）；天津市科技计划项目资助（18YFZCSY00090）