Enhanced ICP-MS detection of 24 elemental impurities in complex, high matrix mineral, medicinal lanthanum carbonates according to ICH Q2 (R2)

Validation of the specificity of ICP-MS methods by ICH Q2 (R2) through spiking experiments cannot characterize the multi-atomic interference of complex high matrix samples, possibly affecting the accuracy of the method and reliability of results. In this study, we highlight this issue by investigating the elemental impurities in lanthanum carbonate raw materials and use isotope ratio analysis to overcome this limitation and establishing an accurate ICP-MS method for 24 elemental impurities (listed in ICH Q3D). An Agilent 7900 ICP-MS was used with an automatic sampler for sample determination in the He mode. The isotope ratio of elemental impurities in the spiked samples was analyzed to characterize polyatomic interference and select the exclusive mass number of elemental impurities. While the recovery rate of most elemental impurities met the requirements, that of selenium (default measurement mass number