Institute of Microbiology of the Czech Academy of Sciences, Prague 4, 142 20, Czech Republic.
Institute of Microbiology of the Czech Academy of Sciences, Prague 4, 142 20, Czech Republic.
Anal Chim Acta. 2019 Oct 31;1078:1-7. doi: 10.1016/j.aca.2019.06.004. Epub 2019 Jun 3.
The novel laser ablation inductively coupled plasma mass spectrometry methodology for the rapid screening of elemental impurities in solid pharmaceutical samples with the daily dose less than 2.0 g has been developed in accordance with requirements of established USP <232/233> chapters and ICH-Q3D guideline. The LA-ICP-MS methodology covering the determination of Cd, Pb, As, Hg, Co, V, Ni, Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag, Pt was successfully validated in terms of linearity, limit of quantification, accuracy, precision, intermediate precision, specificity and range. Moreover, the presented 'in-house' matrix-matched standards preparation methodology helps to overcome crucial analytical problem connected with unavailability of commercial certified matrix-matched reference material suitable for the direct elemental impurities analysis in various kinds of solid pharmaceutical products. A two step homogeneity study of prepared matrix-matched calibration standards is also reported to investigate the homogeneity of distribution of elemental impurities and internal standards across the pressed pellet. The validated LA-ICP-MS method was applied on analysis of several types of solid pharmaceutical samples (active pharmaceutical ingredients, excipients, placebo and final drug products). The proposed method allowed the accurate, precise and fast screening of elemental impurities without necessity of time and labour consuming solutions preparation and thus it can be used in routine practice as an alternative to conventional ICP-MS or ICP-OES for the rapid quality control of different stages of pharmaceutical production.
已开发出一种新颖的激光烧蚀电感耦合等离子体质谱法，用于快速筛选日剂量小于 2.0g 的固体药物样品中的元素杂质，该方法符合已建立的 USP <232/233>章和 ICH-Q3D 指南的要求。涵盖测定 Cd、Pb、As、Hg、Co、V、Ni、Tl、Au、Pd、Ir、Os、Rh、Ru、Se、Ag、Pt 的 LA-ICP-MS 方法已在线性、定量限、准确度、精密度、中间精密度、特异性和范围方面成功得到验证。此外，本文提出的“内部”基质匹配标准制备方法有助于克服与商业认证的基质匹配参考材料有关的关键分析问题，这些参考材料适用于各种固体药物产品中直接的元素杂质分析。还报告了两步均匀性研究，以研究制备的基质匹配校准标准中元素杂质和内标在压片整个过程中的分布均匀性。已验证的 LA-ICP-MS 方法已应用于多种固体药物样品（原料药、赋形剂、安慰剂和最终药物产品）的分析。该方法可实现元素杂质的准确、精密和快速筛选，无需耗时且费力的溶液制备，因此可作为常规 ICP-MS 或 ICP-OES 的替代方法，用于药物生产各个阶段的快速质量控制。
