一种超高效液相色谱-串联质谱法同时测定人血浆样品中 4 种β-内酰胺类抗生素、他唑巴坦和利奈唑胺的方法。

An Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Determination of 4 β-Lactam Antibiotics, Tazobactam, and Linezolid in Human Plasma Samples.

机构信息

Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava.

Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava.

出版信息

Ther Drug Monit. 2022 Dec 1;44(6):784-790. doi: 10.1097/FTD.0000000000001017.

DOI:10.1097/FTD.0000000000001017

PMID:35971670

Abstract

BACKGROUND

Optimization of antimicrobial therapy is a challenge in critically ill patients who develop extreme interindividual and intraindividual pharmacokinetic variability. Therapeutic drug monitoring is a valuable tool for maximizing the effect of a drug and minimizing its adverse and unwanted effects. The aim of the current work was to develop and validate an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine multiple antibiotics in clinical plasma samples from critically ill patients; low sample volume and rapid processing of samples were considered the main criteria.

METHODS

A separation method based on an online combination of UHPLC-MS/MS was developed for the simultaneous determination of 4 β-lactam antibiotics (cefepime, meropenem, cefotaxime, and piperacillin), tazobactam, and linezolid in human plasma samples. The volume of plasma sample used for analysis was 20 µL. The developed method was validated according to Food and Drug Administration guidelines.

RESULTS

The chromatographic run time was 8 minutes. Calibration curves were linear for concentration ranges of 0.1-100 mcg/mL (r 2 > 0.99) for tazobactam, meropenem, cefotaxime, linezolid, and piperacillin and 1-100 mcg/mL (r 2 > 0.99) for cefepime. The intraday and interday accuracy of the method ranged from 92.4% to 110.7% and 93.6% to 113.3%, respectively. The intraday and interday precision values were ≤17.3% and ≤17.4%, respectively. No interfering and carryover analytes were observed.

CONCLUSIONS

The developed UHPLC-MS/MS method is an appropriate and practical tool for therapeutic drug monitoring of the selected antibiotics. Owing to its rapidity, requirement of low sample volume, and high selectivity, sensitivity, and reliability, it can be effectively implemented in routine clinical laboratory tests for critically ill patients.

摘要

背景

在发生极端个体间和个体内药代动力学变异性的重症患者中，优化抗菌治疗是一项挑战。治疗药物监测是最大限度发挥药物作用并最小化其不良和非预期作用的有价值工具。本研究旨在开发和验证一种超高效液相色谱-串联质谱（UHPLC-MS/MS）方法，以测定来自重症患者的临床血浆样本中的多种抗生素；低样本量和快速处理样品被认为是主要标准。

方法

基于 UHPLC-MS/MS 的在线组合，开发了一种分离方法，用于同时测定人血浆样品中的 4 种β-内酰胺类抗生素（头孢吡肟、美罗培南、头孢噻肟和哌拉西林）、他唑巴坦和利奈唑胺。用于分析的血浆样品量为 20 μL。根据美国食品和药物管理局的指南对开发的方法进行了验证。

结果

色谱运行时间为 8 分钟。对于他唑巴坦、美罗培南、头孢噻肟、利奈唑胺和哌拉西林，浓度范围为 0.1-100 mcg/mL（r 2 > 0.99），对于头孢吡肟为 1-100 mcg/mL（r 2 > 0.99），校准曲线呈线性。方法的日内和日间准确度范围分别为 92.4%-110.7%和 93.6%-113.3%。日内和日间精密度值分别为≤17.3%和≤17.4%。未观察到干扰和残留分析物。