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

美罗培南 头孢吡肟 治疗药物监测 他唑巴坦 哌拉西林 色谱法 利奈唑啉 药代动力学 头孢噻肟 抗生素 化学 液相色谱-质谱法 哌拉西林/他唑巴坦 质谱法 药理学 医学 亚胺培南 抗生素耐药性 万古霉素 细菌 铜绿假单胞菌 金黄色葡萄球菌 生物 生物化学 遗传学
作者
Juraj Piešťanský,Ivana Čižmárová,Peter Mikus Prof,Vojtech Parrák,Pavel Babiak,Peter Secnik,Peter Secnik,Andrej Kováč
出处
期刊:Therapeutic Drug Monitoring [Lippincott Williams & Wilkins]
卷期号:44 (6): 784-790 被引量:5
标识
DOI:10.1097/ftd.0000000000001017
摘要

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.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.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.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.
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