Briscoe Chad J, Stiles Mark R, Hage David S
Department of Bioanalysis, MDS Pharma Services, Lincoln, NE 68502, USA.
J Pharm Biomed Anal. 2007 Jun 28;44(2):484-91. doi: 10.1016/j.jpba.2007.03.003. Epub 2007 Mar 13.
System suitability is widely recognized as a critical component of bioanalysis. This paper discusses a generic system suitability test that monitors instrument performance throughout a run when used for liquid chromatography tandem mass spectrometry (LC/MS/MS) in bioanalysis. This system suitability process is designed to ensure that the LC/MS/MS system is performing in a manner that leads to the production of accurate and reproducible data that can be submitted with confidence to regulatory agencies. This process contains tests for signal stability, carryover, and instrument response. This approach is integrated throughout an analytical run and has been used in the analysis of over 25,000 batches of clinical samples. Two case studies are presented in which quality control samples and standards meet all acceptance criteria (based on Standard Operating Procedures and the Food and Drug Administration's recommendations for bioanalytical method validation) but failed the proposed system suitability test, and thus were rejected. In these case studies, the concentrations of a significant number of clinical samples (over 35%) were affected, resulting in changes of more than 15% when the samples were reanalyzed. These data indicate that the poor performance of an LC/MS/MS system could adversely affect the calculated concentrations of unknown samples even though the results for quality control samples appear to be acceptable.
系统适用性被广泛认为是生物分析的关键组成部分。本文讨论了一种通用的系统适用性测试，该测试在生物分析中用于液相色谱串联质谱（LC/MS/MS）时，在整个运行过程中监测仪器性能。此系统适用性过程旨在确保LC/MS/MS系统以能够产生准确且可重现数据的方式运行，这些数据可以放心地提交给监管机构。该过程包含信号稳定性、残留和仪器响应测试。这种方法贯穿于整个分析运行过程中，已用于分析超过25000批临床样本。本文给出了两个案例研究，其中质量控制样品和标准品符合所有验收标准（基于标准操作规程和美国食品药品监督管理局关于生物分析方法验证的建议），但未通过提议的系统适用性测试，因此被拒收。在这些案例研究中，大量临床样本（超过35%）的浓度受到影响，重新分析这些样本时变化超过15%。这些数据表明，即使质量控制样品的结果看似可接受，LC/MS/MS系统的不佳性能仍可能对未知样品的计算浓度产生不利影响。
