LC-MS/MS analysis of five antibiotics in dried blood spots for therapeutic drug monitoring of ICU patients

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-06-07 DOI:10.1016/j.jchromb.2025.124699

Zhan Qi, Sha Zhang, Jie Li, Shijing Qian, Danfei Song, Xiancheng Ye

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Abstract

In the intensive care unit (ICU), optimizing antimicrobial therapy through Therapeutic Drug Monitoring (TDM) can significantly improve patient outcomes. We developed and validated a DBS method for the simultaneous quantification of five antibiotics commonly used in ICUs, namely imipenem, meropenem, tigecycline, teicoplanin, and vancomycin. Dried blood spots (DBS) were prepared by spotting 30 μL of blood onto Whatman 903® cards and analyzed using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). The DBS concentrations measured were compared with serum concentrations analyzed using standard laboratory methods. The paired DBS and serum samples were obtained from ICU. Deming regression and Bland-Altman difference plot were used to assess the consistency between the two methods. The DBS method was validated including selectivity, carryover, precision (0.078–16.70 %), accuracy (85.19–117.17 %), matrix effect, recovery (46.51 %–114.15 %), linearity, and dilution integrity. DBS samples stability at −80 °C for at least 30 days. DBS and serum concentrations of two antibiotics were compared, and statistical analysis confirmed good correlation (r > 0.97) between them. This study provides a new approach to TDM, suggesting that DBS may replace or complement traditional analytical sampling techniques. It has been validated for guiding individualized antimicrobial therapy in ICU patients.

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LC-MS/MS分析5种抗生素用于ICU患者治疗药物监测

在重症监护病房（ICU），通过治疗性药物监测（TDM）优化抗菌药物治疗可显著改善患者预后。我们开发并验证了一种同时定量icu常用的五种抗生素的DBS方法，即亚胺培南、美罗培南、替加环素、替柯planin和万古霉素。将30 μL的血液点染到Whatman 903®卡片上制备干血斑（DBS），并使用超高高效液相色谱-串联质谱（UHPLC-MS/MS）进行分析。将测定的DBS浓度与使用标准实验室方法分析的血清浓度进行比较。配对DBS和血清样本取自ICU。采用Deming回归和Bland-Altman差异图评估两种方法的一致性。对DBS方法进行选择性、延续性、精密度（0.078 ~ 16.70%）、准确度（85.19 ~ 117.17%）、基质效应、回收率（46.51% ~ 114.15%）、线性度和稀释度完整性验证。DBS样品在−80°C下稳定性至少30天。两种抗生素的DBS与血清浓度比较，统计学分析证实相关性良好(r >；0.97)。这项研究为TDM提供了一种新的方法，表明DBS可能取代或补充传统的分析抽样技术。对指导ICU患者个体化抗菌药物治疗具有一定的指导意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.