Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
Department of Toxicology, Canterbury Health Laboratories, Christchurch; and.
Ther Drug Monit. 2022 Dec 1;44(6):709-719. doi: 10.1097/FTD.0000000000000975.
Therapeutic drug monitoring is increasingly being used to optimize beta-lactam antibiotic dosing. Because beta-lactams are inherently unstable, confirming preanalytical sample stability is critical for reporting reliable results. This review aimed to summarize the published literature on the preanalytical stability of selected widely prescribed beta-lactams used in therapeutic drug monitoring.
The published literature (2010-2020) on the preanalytical stability of flucloxacillin, piperacillin, tazobactam, meropenem, cefalexin, cefazolin, and ceftazidime in human plasma, serum, and whole blood was reviewed. Articles examining preanalytical stability at room temperature, refrigerated, or frozen (-20°C) using liquid chromatography with mass spectrometry or ultraviolet detection were included.
Summarizing the available data allowed for general observations to be made, although data were conflicting in some cases (piperacillin, tazobactam, ceftazidime, and meropenem at room temperature, refrigerated, or -20°C) or limited (cefalexin, cefazolin, and flucloxacillin at -20°C). Overall, with the exception of the more stable cefazolin, preanalytical instability was observed after 6-12 hours at room temperature, 2-3 days when refrigerated, and 1-3 weeks when frozen at -20°C. In all cases, excellent stability was detected at -70°C. Studies focusing on preanalytical stability reported poorer stability than studies investigating stability as part of method validation.
Based on this review, as general guidance, clinical samples for beta-lactam analysis should be refrigerated and analyzed within 2 days or frozen at -20°C and analyzed within 1 week. For longer storage times, freezing at -70°C was required to ensure sample stability. This review highlights the importance of conducting well-designed preanalytical stability studies on beta-lactams and other potentially unstable drugs under clinically relevant conditions.
治疗药物监测越来越多地用于优化β-内酰胺类抗生素的给药剂量。由于β-内酰胺类药物本质上不稳定，因此确认分析前样本的稳定性对于报告可靠的结果至关重要。本综述旨在总结已发表的关于在治疗药物监测中广泛使用的选定β-内酰胺类药物的分析前稳定性的文献。
综述了 2010 年至 2020 年期间关于氟氯西林、哌拉西林、他唑巴坦、美罗培南、头孢氨苄、头孢唑林和头孢他啶在人血浆、血清和全血中的分析前稳定性的已发表文献。使用液相色谱-质谱联用或紫外检测法，研究了室温、冷藏或冷冻（-20°C）条件下的分析前稳定性的文章被包括在内。
对可用数据进行总结后可以得出一些一般性的观察结果，但在某些情况下数据存在冲突（室温、冷藏或-20°C 条件下的哌拉西林、他唑巴坦、头孢他啶和美罗培南）或有限（-20°C 条件下的头孢氨苄和头孢唑林以及氟氯西林）。总体而言，除了更稳定的头孢唑林外，室温下 6-12 小时后、冷藏时 2-3 天、冷冻在-20°C 时 1-3 周后，都观察到分析前不稳定。在所有情况下，-70°C 时均检测到极好的稳定性。关注分析前稳定性的研究报告的稳定性比将稳定性作为方法验证一部分的研究报告的稳定性差。
基于本综述，作为一般指导，β-内酰胺类分析的临床样本应冷藏并在 2 天内分析，或冷冻在-20°C 并在 1 周内分析。如需更长的储存时间，则需要在-70°C 下冷冻以确保样品的稳定性。本综述强调了在临床相关条件下对β-内酰胺类药物和其他潜在不稳定药物进行精心设计的分析前稳定性研究的重要性。
