title: Flow injection combined with ICP-MS for accurate high throughput analysis of elemental impurities in pharmaceutical products according to USP <232>/<233>.
abstract: 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 30s and the low sample consumption of below 50 μL, while meeting the strict USP demands on detection/quantification limits, precision and accuracy.
authors.affiliation: Department of Chemistry, University of Natural Resources and Life Sciences, BOKU-Vienna, Vienna, Austria. Electronic address: lisa.fischer@boku.ac.at.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fischer
authors.affiliation: Department of Chemistry, University of Natural Resources and Life Sciences, BOKU-Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zipfel
authors.affiliation: Department of Chemistry, University of Natural Resources and Life Sciences, BOKU-Vienna, Vienna, Austria.
authors.forename: Gunda
authors.initials: G
authors.lastname: Koellensperger
authors.affiliation: AQura GmbH, Rodenbacher Chaussee 4, 63457 Hanau/Wolfgang, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kovac
authors.affiliation: AQura GmbH, Rodenbacher Chaussee 4, 63457 Hanau/Wolfgang, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bilz
authors.affiliation: AQura GmbH, Rodenbacher Chaussee 4, 63457 Hanau/Wolfgang, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kunkel
authors.affiliation: AQura GmbH, Rodenbacher Chaussee 4, 63457 Hanau/Wolfgang, Germany.
authors.forename: Cornel
authors.initials: C
authors.lastname: Venzago
authors.affiliation: Department of Chemistry, University of Natural Resources and Life Sciences, BOKU-Vienna, Vienna, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hann
mesh_terms: D004340:Drug Contamination; D017022:Flow Injection Analysis / Q000379:methods*; D057166:High-Throughput Screening Assays; D013058:Mass Spectrometry; D008670:Metals / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D010602:Pharmacopoeias as Topic; D013054:Spectrophotometry, Atomic / Q000379:methods*
chemical_list: D008670:Metals; D004364:Pharmaceutical Preparations
keywords: EP 5.20; Elemental impurities; ICP-MS inductively coupled plasma mass spectrometry; Pharmaceutical products; USP <232>/<233>