Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany.
Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany.
J Pharmacol Toxicol Methods. 2020 May-Jun;103:106692. doi: 10.1016/j.vascn.2020.106692. Epub 2020 Mar 12.
Ceftolozane is a newer β-lactam antibiotic drug effective against gram-negative pathogens. Its pharmacokinetic parameters are dominated by the patients' kidney function. Consequently, in patients with impaired kidney function or those who are treated with different forms of renal replacement therapy, therapeutic drug monitoring (TDM) of ceftolozane is strongly recommended to enhance safety and efficiency of the antibiotic treatment. Various methods for the quantification of ceftolozane in plasma samples have been described utilizing HPLC-UV or LC-MS/MS. However, all these methods are impaired by the instability of ceftolozane in plasma samples. In this work, we have determined the stability of ceftolozane in human plasma at temperatures of 40 °C, 23 °C, 6 °C and - 20 °C. At 6 °C and - 20 °C, ceftolozane was stable in human plasma over the observed time range of 7 days. At 23 °C and 40 °C, plasma samples were of acceptable (i.e. less than 15% decay) stability over time ranges of 71.2 h and 5.6 h, requiring expedited sample transport to the laboratory. Dried blood spots (DBS) were reported in the literature as matrix with beneficial properties regarding stabilities of β-lactam antibiotics. However, in this study we found that ceftolozane was of inferior stability in this matrix in comparison to plasma. Thus, DBS cannot be recommended as matrix for ceftolozane in TDM.
头孢洛扎是一种新型的β-内酰胺类抗生素药物，对革兰氏阴性病原体有效。其药代动力学参数主要受患者肾功能的影响。因此，在肾功能受损的患者或接受不同形式肾脏替代治疗的患者中，强烈建议进行头孢洛扎的治疗药物监测（TDM），以提高抗生素治疗的安全性和效率。已经描述了利用 HPLC-UV 或 LC-MS/MS 定量检测血浆样品中头孢洛扎的各种方法。然而，所有这些方法都受到头孢洛扎在血浆样品中不稳定性的影响。在这项工作中，我们确定了头孢洛扎在 40°C、23°C、6°C 和-20°C 下在人血浆中的稳定性。在 6°C 和-20°C 下，头孢洛扎在人血浆中在观察到的 7 天时间范围内稳定。在 23°C 和 40°C 下，血浆样品在 71.2 h 和 5.6 h 的时间范围内具有可接受的（即小于 15%衰减）稳定性，需要尽快将样品运送到实验室。文献中报道了干血斑（DBS）作为具有β-内酰胺类抗生素稳定性有益特性的基质。然而，在这项研究中，我们发现与血浆相比，头孢洛扎在这种基质中的稳定性较差。因此，DBS 不能作为 TDM 中头孢洛扎的基质推荐。
