Screening of 12 elemental impurities in pharmaceutical excipient grades of titanium dioxide from various sources and their correlations with whiteness
In the process of promoting the implementation and transformation of the Q3D guideline of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH)in China,the risk assessment of elemental impurities in naturally sourced excipients often faces challenges such as multiple types of elemental impurities and insufficient detection methods.In this paper,an inductively coupled plasma mass spectrometry(ICP-MS)method for screening 12 elemental impurities in titanium dioxide was established using the optimized acid extraction pre-treatment method.The accuracy and repeatability of the method were good.The recoveries of cadmium,lead,mercury,cobalt,nickel,lithium,barium,molybdenum,copper,chromium and iron were 83.6％-101.6％,the recovery of antimony was 54.1％,and the RSD was 1.1％-10.2％(n=6).The evaluation results of elemental impurities showed that the risk of cadmium,mercury,cobalt,nickel,lithium,barium,molybdenum,copper,chromium and antimony was low,while the risk of lead was high,and it is recommended that a lead salt test be added to the pharmacopoeia standard for this product.Based on the statistical data,the differences in the control levels of elemental impurities and whiteness of 29 batches of titanium dioxide samples from 10 domestic and foreign manufacturers were compared and analyzed.The Pearson correlation coefficient method was used to analyze the correlation between residual elemental impurities and whiteness,and a heat map was used to visualize the results.The results showed that whiteness was significantly negatively correlated with the amount of residual barium and the sum of residual elemental impurities.It is suggested that the manufactures should include whiteness as an internally controlled indicator to further improve the quality of titanium dioxide used as a pharmaceutical excipient.
pharmaceutical excipienttitanium dioxideinductively coupled plasma mass spectrometry(ICP-MS)elemental impurity
万方数据
维普
