Strege Mark A
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Anal Chem. 2009 Jun 1;81(11):4576-80. doi: 10.1021/ac900441k.
Ion mobility spectrometry (IMS) is a technique attractive for use within the pharmaceutical industry for at-line determination of residues on swabs taken from the surfaces of manufacturing equipment for the purposes of cleaning validation or verification. In this study, the development of a novel IMS method to provide a measurement of total residue present on a swab is described. The technique is based upon quantitation of charged atmospheric gas reactant ion consumption (RIC) within the instrument as a direct measure of the mass of total ionizable residue. Coupled with the conventional analysis of the active pharmaceutical ingredient within a single 2 min analysis, RIC determination provided the benefit of a single measure representative of the presence of multiple residue components or unknown components. To account for differences in response between components of a model drug product (Cymbalta) and its associated cleaning agents, a strategy was proposed to determine a "worst case" total residue test result based on RIC. A limitation of the IMS method was its incompatibility with cleaners containing a high concentration of inorganic components. The methodology provided a range from 5-50 microg per 25 cm(2) surface area and acceptable analyte recovery (50-100%).
离子迁移谱（IMS）是一种在制药行业颇具吸引力的技术，可用于在线测定从生产设备表面采集的拭子上的残留物，以进行清洁验证或确认。在本研究中，描述了一种新型IMS方法的开发，该方法用于测量拭子上存在的总残留物。该技术基于对仪器内带电大气气体反应物离子消耗（RIC）的定量分析，以此作为总可电离残留物质量的直接测量方法。结合在单次2分钟分析中对活性药物成分的常规分析，RIC测定具有单一测量的优势，可代表多种残留成分或未知成分的存在情况。为了解释模型药品（度洛西汀）及其相关清洁剂各成分之间响应的差异，提出了一种基于RIC确定“最坏情况”总残留测试结果的策略。IMS方法的一个局限性是它与含有高浓度无机成分的清洁剂不兼容。该方法提供了每25平方厘米表面积5 - 50微克的测量范围以及可接受的分析物回收率（50 - 100%）。
