目的:建立电感耦合等离子体质谱(ICP-MS)法测定酮咯酸氨丁三醇注射液中Al、As、B、Ca、Cd、Fe、Mn、Pb、Sb、Si、Ti共11种元素杂质的迁移量,并对酮咯酸氨丁三醇注射液中上述元素含量进行测定,做出初步的风险评估。方法:样品经浓硝酸处理后滤去沉淀,用1%硝酸稀释并定容。在标准溶液中加入2%乙醇基体,通过基体匹配法结合在线多元素内标校正消除基质效应,并通过氢气反应模式与氦气碰撞模式消除多原子离子干扰。结果:11种元素线性关系良好(r≥0.997 0),检测限为0.049~133 ng·mL-1,各元素的平均加样回收率为83.8%~107.1%,重复性RSD为2.6%~11.0%。对3个批次的加速试验样品进行了测定,安全性风险较低。结论:ICP-MS基体匹配法简便、快速、准确,可有效消除基质效应,可用于酮咯酸氨丁三醇注射液中11种元素杂质的测定,并为药包材相容性的风险评估提供技术参考。
Objective: To develop an inductively coupled plasma mass spectrometry (ICP-MS) matrix matching method for determination of migration of 11 elements in ketorolac tromethamine injection, including Al, As, B, Ca, Cd, Fe, Mn, Pb, Sb, Si, Ti. Methods: Samples were diluted and capacitated with 1% nitric acid after precipitation with nitric acid. 2% ethanol was added into the standard solution as the matrix. The matrix effect was eliminated by the matrix matching method, and the polyatomic ion interferences were eliminated by the hydrogen collision reaction mode and the helium collision mode. Results: The linearity of 11 elements was good (r≥0.997 0). The limits of detection were 0. 049-133 ng·mL-1. The average recoveries of all 11 elements were in the range of 83.8%-107.1%, and the RSD of repeatability was 2.6%-11.0%. Three batches of ketorolac tromethamine injection under acceleration were tested. The overall safety risk was low. Conclusion: The established matrix matching ICP-MS method is simple, rapid and accurate. It can effectively eliminate the matrix effect and be used for the determination of eleven elemental impurities in ketorolac tromethamine injection, providing technical reference for risk assessment of drug packaging material compatibility.
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