LC-MS/MS生物分析中试验样品再分析失败后的调查和解决方案

试验样品再分析(ISR)如今已普遍用于法规依从的生物分析实验室,是评估生物分析方法的重现性、可靠性和准确度的基本措施之一。虽然统计数据显示,LC-MS/MS生物分析中95%以上的ISR符合接受标准,然而失败时依然值得进行充分的科学调查与评估,以发现其根本原因。本文从稳定性问题、人为因素、样品处理过程、方法固有缺陷等方面对小分子化学药物的ISR失败原因进行分类分析,并举例讨论ISR影响因素及改进措施,列出ISR失败后需查根溯源,重测ISR,撰写调查报告并分享讨论等调查流程,并就如何降低ISR失败率提出法规依从,充分了解化合物特性,使用真实样品考察稳定性的解决方案,最后对其前景进行展望。

Incurred sample reanalysis(ISR), which is now widely applied in regulated bioanalytical laboratories, can serve as a measure of the reproducibility, robustness and accuracy of bioanalytical methods. Even with an average ISR success rate of 95% or higher and an increasing number of ISR tests being conducted in LC-MS/MS assays, more and more situations deserve scientific evaluation or investigation for the unmatched reassay results to reveal the cause.The purpose of this thesis is to classify the factors in ISR failure investigations for small molecule medicines the terms of instability of drug/metabolites, human error, sample processing and method error.Five case studies, were described where incurred sample reanalysis failure were encountered.The following approaches were listed, including cause identification, ISR reanalysis, document investigation and group discussion.Which could be taken to elucidate the failure.Meanwhile, the following remedial actions were proposed, including the regulatory compliance bioanalysis, thorough study of the analyte, and application of real samples in stability determination.Finally, the perspective of ISR in future was discussed.