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    ICP-MS测定注射用亚锡甲氧异腈中16种元素杂质含量

    Determination of Contents of 16 Elemental Impurities in Methoxy Isobutyl Isonitrile and Stannous Chloride for Injection by ICP-MS

      摘要
    • 摘要:
      目的 建立电感耦合等离子体质谱法(inductively coupled plasma-mass spectrometry，ICP-MS)测定注射用亚锡甲氧异腈中元素杂质的含量。
      方法 样品溶解后，采用ICP-MS半定量测定模式对注射用亚锡甲氧异腈中元素杂质进行初步筛查，结合国际人用药品注册技术协调会(International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use，ICH)Q3D 元素杂质指导原则的要求，确定 16 种元素：锂(Li)、镁(Mg)、铝(Al)、硅(Si)、钾(K)、钒(V)、铁(Fe)、钴(Co)、镍(Ni)、锌(Zn)、砷(As)、镉(Cd)、铟(In)、锑(Sb)、汞(Hg)和铅(Pb)作为定量考察和控制的元素杂质研究对象。ICP-MS 采集模式选择动能歧视模式进行定量方法研究，分别以钪(Sc)、锗(Ge)、钇(Y)、铋(Bi)作为内标，测定16种元素杂质的含量。
      结果 16种元素杂质在各自线性范围内响应与浓度相关性良好(r≥0.9993)；方法精密度(RSD≤3.53%)和重复性(RSD≤3.69%)均较好；各元素平均回收率为 95.86%~105.64%(RSD≤5.06%，n=9)，方法准确性良好。注射用亚锡甲氧异腈样品中16种元素均未超出限度，Mg、K、Zn 3种元素含量相对较高。
      结论 金属盐类制剂产品可能引入 ICH Q3D 原则要求以外的元素杂质。本研究建立的 ICP-MS定量方法简便、快速，可用于注射用亚锡甲氧异腈中元素杂质的筛查、检测和风险评估。

       

      Abstract:
      OBJECTIVE To establish an inductively coupled plasma-mass spectrometry(ICP-MS) method for the determination of elemental impurities in methoxy isobutyl isonitrile and stannous chloride for injection.
      METHODS The ICP-MS semi-quantitative determination mode was used to conduct a preliminary screening of elemental impurities in methoxy isobutyl isonitrile and stannous chloride for injection after the samples were dissolved. In accordance with the requirements of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) Q3D guidelines for elemental impurities, there were 16 elements: Li, Mg, Al, Si, K, V, Fe, Co, Ni, Zn, As, Cd, In, Sb, Hg and Pb, which were chosen as the research objects of elemental impurities for quantitative investigation. The kinetic energy discrimination mode was selected for the ICP-MS collection mode while Sc, Ge, Y, and Bi were used as internal standards respectively. The contents of 16 elemental impurities were determined.
      RESULTS The impurities of each element were within the linear ranges and the responses had a good correlation with the concentration(r≥0.9993). The precision(RSD≤3.53%) and repeatability(RSD≤3.69%) of the method met the requirements, with the average recoveries of these elements ranging from 95.86% to 105.64%(RSD≤5.06%, n=9), and the accuracy was good. None of the 16 elements exceeded the specified limits, with Mg, K and Zn present at relatively higher levels in methoxy isobutyl isonitrile and stannous chloride for injection.
      CONCLUSION Metal salts may introduce impurities of element other than those required by the ICH Q3D guidelines. The ICP-MS method established in this study is simple and rapid, and can meet the requirements for the screening, detection and risk assessment of elemental impurities in methoxy isobutyl isonitrile and stannous chloride for injection.

       

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