Simultaneous determination of three β-Lactam/β-lactamase inhibitor combinations in critically ill patients by UPLC-MS/MS

IF 2.8 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Journal of Chromatography B Pub Date : 2025-01-15 DOI:10.1016/j.jchromb.2024.124431
Xiaoyang Liu , Bo Li , Shu Li , Xiaoxue Wang , Xudong Kong , Yue Chen , Qian Zhang , Jun Duan , Wenqian Chen , Pengmei Li
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Abstract

β-Lactam/β-lactamase inhibitors (BL/BLIs) are widely used in critically ill patients. Recent research has shown the importance of therapeutic drug monitoring (TDM) of BLs, but few studies have highlighted the importance of detecting BLIs in critically ill patients. In our laboratory, we have developed and validated a simple and robust method for the determination of ceftazidime, cefoperazone, piperacillin, avibactam, sulbactam and tazobactam in human plasma by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Sample preparation was by protein precipitation of 100 µL of sample, followed by chromatographic separation on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) and mass spectrometric detection using a SHIMADZU 8050CL in multiple reaction monitoring (MRM) mode. The method was fully validated for selectivity, carry-over, linearity, lower limit of quantification, matrix effect, extraction recovery, stability and dilution integrity. The results of the TDM could provide feedback to clinicians and allow timely adjustment of dosing regimens in critically ill patients. The method is suitable for routine TDM and has been successfully applied to the clinical determination of 81 plasma concentrations in 44 patients.
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UPLC-MS/MS同时测定危重患者中3种β-内酰胺/β-内酰胺酶抑制剂组合。
β-内酰胺/β-内酰胺酶抑制剂(BL/BLIs)广泛应用于危重患者。近年来的研究显示了bli的治疗药物监测(TDM)的重要性,但很少有研究强调在危重患者中检测bli的重要性。本实验室建立并验证了一种高效液相色谱-串联质谱法(UPLC-MS/MS)测定人血浆中头孢他啶、头孢哌酮、哌拉西林、阿维巴坦、舒巴坦和他唑巴坦的简便易行方法。样品制备采用蛋白沉淀100µL样品,采用ACQUITY UPLC®BEH C18色谱柱(2.1 × 50 mm, 1.7µm)进行色谱分离,采用SHIMADZU 8050CL在多反应监测(MRM)模式下进行质谱检测。对该方法的选择性、携带性、线性、定量下限、基质效应、提取回收率、稳定性和稀释完整性进行了充分验证。TDM的结果可以为临床医生提供反馈,并允许及时调整危重患者的给药方案。该方法适用于常规TDM,已成功应用于临床测定44例患者81例血药浓度。
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来源期刊
Journal of Chromatography B
Journal of Chromatography B 医学-分析化学
CiteScore
5.60
自引率
3.30%
发文量
306
审稿时长
44 days
期刊介绍: The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.
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