The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry
Introduction: Pharmaceutical laboratories experienced a paradigm shift in drug product elemental impurity (EI) expectations in International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline Q3D and United States Pharmacopeia (USP) General Chapters...
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Elsevier
2025-06-01
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| Series: | Journal of Trace Elements and Minerals |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773050625000187 |
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| author | James M. Harrington Donna S. Seibert Glenn Williams Thanh Nguyen Denise McClenathan Stephen W. Erickson |
| author_facet | James M. Harrington Donna S. Seibert Glenn Williams Thanh Nguyen Denise McClenathan Stephen W. Erickson |
| author_sort | James M. Harrington |
| collection | DOAJ |
| description | Introduction: Pharmaceutical laboratories experienced a paradigm shift in drug product elemental impurity (EI) expectations in International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline Q3D and United States Pharmacopeia (USP) General Chapters <232>/<233>. These guidelines describe a risk-based approach to EI analysis. Few systematic evaluations of interlaboratory performance on EI analysis in pharmaceutics have been conducted following these guidelines. Our goal is to address key technical challenges faced by laboratories during the implementation of these regulations. Materials and Methods: We organized an interlaboratory study using standardized samples and methodology to assess sample preparation and analysis variability. Participants performed microwave-assisted acid preparation of simulated pharmaceutical products and analyzed Class 1 and 2A EI's by inductively-coupled plasma-mass spectrometry (ICP-MS). Several laboratories performed X-ray Fluorescence spectroscopy (XRF) for comparison. Results: ICP-MS reproducibility was high both within and between laboratories, except for Hg and V. Exhaustive extraction and total digestion were generally comparable, between 87 and 111 % for As, Cd, Co, and Pb. Total digestion exhibited lower variability than exhaustive extraction. Two types of microwave systems produced comparable results for most elements except Hg and Pb. The summation approach was comparable to direct analysis of tablets except for Hg and Cd, but summation demonstrated greater variability. XRF showed good agreement with ICP-MS and low replicate variability within labs. Discussion and Conclusions: While the results were generally favorable, they demonstrate that some technical challenges remain to be addressed related to standardizing laboratory practices including interference correction strategies and selection of preparation methods. We discuss implications for method transfer between laboratories. |
| format | Article |
| id | doaj-art-8cdcaa636fb54bd6baa02148cc44387c |
| institution | Kabale University |
| issn | 2773-0506 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Trace Elements and Minerals |
| spelling | doaj-art-8cdcaa636fb54bd6baa02148cc44387c2025-08-20T03:53:07ZengElsevierJournal of Trace Elements and Minerals2773-05062025-06-011210022710.1016/j.jtemin.2025.100227The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industryJames M. Harrington0Donna S. Seibert1Glenn Williams2Thanh Nguyen3Denise McClenathan4Stephen W. Erickson5RTI International, Research Triangle Park, NC, United States of America; Corresponding author at: 3040 E. Cornwallis Rd. P.O. Box 12194 Research Triangle Park, NC, 27709.Perrigo Company, Allegan, MI, United States of AmericaRigaku Corporation, The Woodlands, TX, United States of America; VPrep Corp., Houston, TX, United States of AmericaRigaku Corporation, The Woodlands, TX, United States of America; VPrep Corp., Houston, TX, United States of AmericaProcter and Gamble, Cincinnati, OH, United States of AmericaRTI International, Research Triangle Park, NC, United States of AmericaIntroduction: Pharmaceutical laboratories experienced a paradigm shift in drug product elemental impurity (EI) expectations in International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline Q3D and United States Pharmacopeia (USP) General Chapters <232>/<233>. These guidelines describe a risk-based approach to EI analysis. Few systematic evaluations of interlaboratory performance on EI analysis in pharmaceutics have been conducted following these guidelines. Our goal is to address key technical challenges faced by laboratories during the implementation of these regulations. Materials and Methods: We organized an interlaboratory study using standardized samples and methodology to assess sample preparation and analysis variability. Participants performed microwave-assisted acid preparation of simulated pharmaceutical products and analyzed Class 1 and 2A EI's by inductively-coupled plasma-mass spectrometry (ICP-MS). Several laboratories performed X-ray Fluorescence spectroscopy (XRF) for comparison. Results: ICP-MS reproducibility was high both within and between laboratories, except for Hg and V. Exhaustive extraction and total digestion were generally comparable, between 87 and 111 % for As, Cd, Co, and Pb. Total digestion exhibited lower variability than exhaustive extraction. Two types of microwave systems produced comparable results for most elements except Hg and Pb. The summation approach was comparable to direct analysis of tablets except for Hg and Cd, but summation demonstrated greater variability. XRF showed good agreement with ICP-MS and low replicate variability within labs. Discussion and Conclusions: While the results were generally favorable, they demonstrate that some technical challenges remain to be addressed related to standardizing laboratory practices including interference correction strategies and selection of preparation methods. We discuss implications for method transfer between laboratories.http://www.sciencedirect.com/science/article/pii/S2773050625000187Elemental impuritiesMethod developmentInterlaboratory studyUSP 232/233ICH Q3D |
| spellingShingle | James M. Harrington Donna S. Seibert Glenn Williams Thanh Nguyen Denise McClenathan Stephen W. Erickson The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry Journal of Trace Elements and Minerals Elemental impurities Method development Interlaboratory study USP 232/233 ICH Q3D |
| title | The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry |
| title_full | The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry |
| title_fullStr | The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry |
| title_full_unstemmed | The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry |
| title_short | The Product Quality Research Institute elemental impurity interlaboratory study: Results and implications for industry |
| title_sort | product quality research institute elemental impurity interlaboratory study results and implications for industry |
| topic | Elemental impurities Method development Interlaboratory study USP 232/233 ICH Q3D |
| url | http://www.sciencedirect.com/science/article/pii/S2773050625000187 |
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