| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1221354 | Journal of Pharmaceutical and Biomedical Analysis | 2014 | 9 Pages |
•State-of-the-art methodology for elemental impurity analysis in pharmaceuticals.•Application of flow injection analysis for unprecedented high sample throughput.•Cost reductive benefits due to low consumption of sample and high purity chemicals.
New guidelines of the United States Pharmacopeia (USP), European Pharmacopeia (EP) and international organization (ICH, International Conference on Harmonization) regulating elemental impurity limits in pharmaceuticals seal the end of unspecific analysis of metal(oid)s as outlined in USP <231> and EP 2.4.8. Chapter USP <232> and EP 5.20 as well as drafts from ICH Q3D specify both daily doses and concentration limits of metallic impurities in pharmaceutical final products and in active pharmaceutical ingredients (API) and excipients. In chapters USP <233> and EP 2.4.20 method implementation, validation and quality control during the analytical process are described. By contrast with the – by now – applied methods, substance specific quantitative analysis features new basic requirements, further, significantly lower detection limits ask for the necessity of a general changeover of the methodology toward sensitive multi element analysis by ICP-AES and ICP-MS, respectively.A novel methodological approach based on flow injection analysis and ICP-SFMS/ICP-QMS for the quick and accurate analysis of Cd, Pb, As, Hg, Ir, Os, Pd, Pt, Rh, Ru, Cr, Mo, Ni, V, Cu, Mn, Fe and Zn in drug products by prior dilution, dissolution or microwave assisted closed vessel digestion according to the regulations is presented. In comparison to the acquisition of continuous signals, this method is advantageous with respect to the unprecedented high sample throughput due to a total analysis time of approximately 30 s and the low sample consumption of below 50 μL, while meeting the strict USP demands on detection/quantification limits, precision and accuracy.
Graphical abstractFlow injection peak obtained via FI-ICP-QMS for an injection volume of 10 μL of a standard solution containing 1 μg L−1 Pt.Figure optionsDownload full-size imageDownload as PowerPoint slide
