Measurement Uncertainty Estimation for the Quantitative Determination of Elemental Impurities in Active Pharmaceutical Ingredients Using Microwave Digestion Followed by ICP-OES According to USP <232> and <233> Specifications

The elemental impurities present in the active pharmaceutical ingredient (API) possess toxicological effect without providing any therapeutic benefits to the patients. To prevent the risk factors associated with these impurities, Food and Drug Administration in collaboration with United States Pharmacopeia Convention and International Council for Harmonisation (ICH) organizations has issued new guidelines which regulate the limit of elemental impurities in API and excipients. Therefore, the monitoring of trace elemental content in API becomes a crucial factor during the manufacturing process. Hence, in the given framework, we have standardized a simple and accurate method for the quantitative estimation of 41 elemental impurities present in the API samples using inductively coupled plasma–optical emission spectroscopy with measurement uncertainty estimation according to USP <232> and <233> specifications. Measurement uncertainty recognizes and quantifies the practicable error during the analysis and produce the combining result of total uncertainty. The proposed method showed dynamic linearity in the concentration range of 0.003–0.500 µg/g with a coefficient of determination between 0.9552 and 0.9999. The limit of detection and limit of quantification were ranged 0.0006–0.0130 µg/g and 0.0020–0.0431 µg/g, respectively. Recoveries obtained from 70 to 120% and precision values were acceptable as per guidelines. The results of relative expanded uncertainty Urel (k = 2) values lied in the range of 3.02–15.88% in API samples. Method recovery, precision and purity of the standards have been identified as major uncertainty sources.