Barone Rossella, Conti Matteo, Cojutti Pier Giorgio, Gatti Milo, Viale Pierluigi, Pea Federico
Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero Universitaria of Bologna, 40138 Bologna, Italy.
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy.
Antibiotics (Basel). 2023 Jan 19;12(2):213. doi: 10.3390/antibiotics12020213.
Cefiderocol (C) is a parenteral siderophore cephalosporin with relevant inter-individual pharmacokinetic variability among critically ill patients, which may potentially affect effective drug exposure. Therapeutic drug monitoring (TDM) may concur in improving the real-time management of C therapy in clinics. In this study, we developed and validated a fast and sensitive Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry (LC-ITD-MS/MS) method for measuring C in human plasma microsamples, as small as 3 microliters. Analysis was preceded by a user-friendly pre-analytical single-step and was performed by means of a very fast chromatographic run of 4 min, followed by positive electrospray ionization and detection on a high sensitivity triple quadrupole tandem mass spectrometer operated in multiple reaction monitoring mode. The straightforward analytical procedure was successfully validated, based on the European Medicines Agency (EMA) guidelines, in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and stability. The novel method was successfully applied to TDM of C in more than 50 cases of critically carbapenem-resistant Gram-negative bacterial infections and enabled us to optimize antibiotic therapy.
头孢地尔（C）是一种肠外铁载体头孢菌素，在重症患者中存在个体间药代动力学差异，这可能会影响药物有效暴露。治疗药物监测（TDM）可能有助于改善临床中C治疗的实时管理。在本研究中，我们开发并验证了一种快速灵敏的液相色谱-同位素稀释串联质谱（LC-ITD-MS/MS）方法，用于测量低至3微升的人血浆微量样品中的C。分析前采用用户友好的单步前分析步骤，并通过4分钟的快速色谱运行进行，随后进行正电喷雾电离，并在以多反应监测模式运行的高灵敏度三重四极杆串联质谱仪上进行检测。根据欧洲药品管理局（EMA）指南，该简单的分析程序在特异性、灵敏度、线性、精密度、准确度、基质效应、提取回收率、定量限和稳定性方面成功得到验证。该新方法已成功应用于50多例耐碳青霉烯类革兰氏阴性菌严重感染患者的C的TDM，并使我们能够优化抗生素治疗。
