Barone Rossella, Conti Matteo, Cojutti Pier Giorgio, Gatti Milo, Viale Pierluigi, Pea Federico
SSD Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, 40138 Bologna, Italy.
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy.
Pharmaceutics. 2023 Feb 1;15(2):480. doi: 10.3390/pharmaceutics15020480.
Dalbavancin (DBV) is a long-acting antistaphylococcal lypoglycopeptide that is being increasingly used for long-term treatment of a wide range of subacute and/or chronic infections, mainly osteo-articular infections (OAI). Population pharmacokinetic studies showed that two 1500 mg doses 1 week apart can ensure effective treatment for several weeks. In this scenario, therapeutic drug monitoring (TDM) can be a helpful tool for providing clinicians with real-time feedback on the duration of optimal treatment by measuring drug concentrations over time in each single patient. The aim of this study was to develop and validate a fast and simple analytical method based on the Liquid Chromatography-Isotope Dilution Tandem Mass Spectrometry (ITD LC-MS/MS) technique for measuring DBV concentrations in human plasma microsamples. It will allow an innovative, very convenient and minimally invasive way of sampling. Analysis was performed by simple single-step sample preparation and very short instrumental run time (4 min). Analytical performance met all criteria in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, dilution integrity and stability under different conditions set by the European Medicines Agency (EMA) for drug quantification by means of bioanalytical methods. The method was successfully applied for measuring DBV concentrations (range = 2.0-77.0 mg/L) in a cohort of patients receiving long-term DBV treatment of subacute and/or chronic infections.
达巴万星（DBV）是一种长效抗葡萄球菌糖肽，越来越多地用于多种亚急性和/或慢性感染的长期治疗，主要是骨关节炎感染（OAI）。群体药代动力学研究表明，相隔1周给予两次1500 mg剂量可确保数周的有效治疗。在这种情况下，治疗药物监测（TDM）可以成为一种有用的工具，通过在每个患者中随时间测量药物浓度，为临床医生提供关于最佳治疗持续时间的实时反馈。本研究的目的是开发并验证一种基于液相色谱-同位素稀释串联质谱（ITD LC-MS/MS）技术的快速简便分析方法，用于测量人血浆微量样本中的DBV浓度。它将提供一种创新、非常方便且微创的采样方式。通过简单的单步样品制备和非常短的仪器运行时间（4分钟）进行分析。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、稀释完整性以及在欧洲药品管理局（EMA）规定的不同条件下通过生物分析方法进行药物定量的稳定性方面，分析性能均符合所有标准。该方法已成功应用于测量接受亚急性和/或慢性感染长期DBV治疗的一组患者中的DBV浓度（范围 = 2.0 - 77.0 mg/L）。
