Abstract：
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.
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.
摘要：
治疗药物监测越来越多地用于优化β-内酰胺抗生素给药。因为β-内酰胺本质上是不稳定的，确认分析前样品的稳定性对于报告可靠的结果至关重要。这篇综述旨在总结已发表的有关用于治疗药物监测的选定广泛处方的β-内酰胺的分析前稳定性的文献。
关于氟氯西林的预分析稳定性的已发表文献（2010-2020），哌拉西林,他唑巴坦,美罗培南,头孢氨苄,头孢唑啉,和人血浆中的头孢他啶,血清,并对全血进行了检查。在室温下检查分析前稳定性的文章，冷藏,或冷冻（-20°C）使用液相色谱和质谱或紫外线检测包括在内。
总结允许进行一般观察的可用数据，尽管在某些情况下数据相互矛盾(哌拉西林，他唑巴坦,头孢他啶,和美罗培南在室温下，冷藏,或-20°C)或限制(头孢氨苄，头孢唑啉,和氟氯西林在-20℃)。总的来说,除了更稳定的头孢唑啉，在室温下6-12小时后观察到分析前不稳定性，冷藏2-3天，-20℃冷冻1-3周在所有情况下,在-70°C下检测到优异的稳定性。专注于分析前稳定性的研究报告的稳定性比研究方法验证的稳定性差。
根据这篇综述，作为一般指导，用于β-内酰胺分析的临床样本应在2天内冷藏并分析,或在-20°C下冷冻并在1周内分析.对于更长的存储时间，需要在-70°C下冷冻以确保样品稳定性。这篇综述强调了在临床相关条件下对β-内酰胺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。
关于氟氯西林的预分析稳定性的已发表文献（2010-2020），哌拉西林,他唑巴坦,美罗培南,头孢氨苄,头孢唑啉,和人血浆中的头孢他啶,血清,并对全血进行了检查。在室温下检查分析前稳定性的文章，冷藏,或冷冻（-20°C）使用液相色谱和质谱或紫外线检测包括在内。
总结允许进行一般观察的可用数据，尽管在某些情况下数据相互矛盾(哌拉西林，他唑巴坦,头孢他啶,和美罗培南在室温下，冷藏,或-20°C)或限制(头孢氨苄，头孢唑啉,和氟氯西林在-20℃)。总的来说,除了更稳定的头孢唑啉，在室温下6-12小时后观察到分析前不稳定性，冷藏2-3天，-20℃冷冻1-3周在所有情况下,在-70°C下检测到优异的稳定性。专注于分析前稳定性的研究报告的稳定性比研究方法验证的稳定性差。
根据这篇综述，作为一般指导，用于β-内酰胺分析的临床样本应在2天内冷藏并分析,或在-20°C下冷冻并在1周内分析.对于更长的存储时间，需要在-70°C下冷冻以确保样品稳定性。这篇综述强调了在临床相关条件下对β-内酰胺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。
