The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry
Year: 2025
Type: article
Abstract: The pharmaceutical industry recently experienced a paradigm shift in drug product elemental impurity (EI) analysis in ICH Q3D Guidelines and USP General Chapters <232> and <233>, which allow for a risk-based approach to EI analysis by inductively-coupled plasma-mass spectrometry (ICP-MS) and similar techniques. There have been few systematic evaluations of interlaboratory performance on EI analysis in drug products since the implementation of EI guidelines. We organized an interlaboratory study to address key technical challenges faced by laboratories during their implementation, including laboratory equipment, interference correction strategies, and the method of calculating the final concentrations.Reproducibility was good for most analytes, both within and between laboratories. Although there were some problematic elements, most notably Hg and V, participant labs generally produced consistent results. Exhaustive extraction and total digestion exhibited comparable mean concentrations for many analytes and materials, within 87-111% of each other for As, Cd, Co, and Pb. Total digestion exhibited lower variability than exhaustive extraction. SRC and IPV microwave systems produced comparable results for most elements except Hg and Pb. The summation approach demonstrated comparable results with direct analysis of tablets for most analytes except Hg and Cd, but summation demonstrated greater variability for most analytes. While the results were generally favorable, they also demonstrate that after the implementation of ICH Q3D and USP <232>/<233>, some technical challenges remain to be addressed, related to standardizing laboratory practices and adoption of best practices, including interference correction strategies and method transfer between laboratories.
Authors: James M. Harrington, Donna S. Seibert, Glenn Williams, Thanh Nguyen, Denise McClenathan, Stephen W. Erickson
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,910
OpenAlex ID: W4408262093