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

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.