目的 采用電感耦合等離子體質(zhì)譜（ICP-MS）法測定甲磺酸卡莫司他原料藥中鎘（Cd）、鉛（Pb）、砷（As）、汞（Hg）、鈷（Co）、礬（V）、鎳（Ni）、鉻（Cr）8種無機元素的含量。方法 用微波消解進(jìn)行樣品前處理；以⁷³Ge、¹¹⁵In、²⁰⁹Bi為內(nèi)標(biāo)，采用ICP-MS進(jìn)行測定，射頻功率1 550 W，霧化氣流量1.1 L·min^-1，霧化室溫度2.7℃，測量模式為碰撞池模式（KED），碰撞氣體積流量4.3 mL·min^-1，冷卻氣體積流量14.0 L·min^-1，輔助氣體積流量0.8 L·min^-1，泵速40 r·min^-1。結(jié)果 8種元素標(biāo)準(zhǔn)曲線的相關(guān)系數(shù)均大于0.990；加樣回收率在88.9%~124.7%（n=3）；重復(fù)性試驗RSD為0.9%~2.3%（n=6）；中間精密度試驗RSD為1.0%~13.8%（n=12），均滿足USP<233>方法學(xué)驗證的要求。樣品檢測的結(jié)果遠(yuǎn)小于國際人用藥物注冊技術(shù)協(xié)調(diào)會議《元素雜質(zhì)指導(dǎo)原則Q3D》（ICH Q3D）中各無機元素的每日允許暴露量（PDE）。結(jié)論 建立的ICP-MS法樣品用量少，分析速度快、靈敏度高，可用于甲磺酸卡莫司他原料藥中無機元素的含量測定。

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

中國醫(yī)學(xué)科學(xué)院醫(yī)學(xué)與健康科技創(chuàng)新工程項目資助（2019-I2M-5-020）；天津市科技計劃項目資助（18YFZCSY00090）