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UPLC–MS/MS method for therapeutic drug monitoring of 10 antibiotics used in intensive care units
Author(s) -
ElNajjar Nahed,
Hösl Julian,
Holzmann Thomas,
Jantsch Jonathan,
Gessner André
Publication year - 2018
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2253
Subject(s) - cefepime , meropenem , piperacillin , therapeutic drug monitoring , ampicillin , chromatography , ceftazidime , trimethoprim , chemistry , antibiotics , ertapenem , protein precipitation , pharmacokinetics , imipenem , pharmacology , medicine , high performance liquid chromatography , biochemistry , antibiotic resistance , biology , bacteria , pseudomonas aeruginosa , genetics
A large variation in the levels of different ß‐lactams and other antibiotics used in critically ill patients has been documented. The aim of this study is to establish and validate a fast, ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous analysis of ten antibiotics (Meropenem, Cefepime, Ceftazidime, Piperacillin, Benzylpenicillin, Ampicillin, Flucloxacillin, Linezolid, and Sulfamethoxazole/Trimethoprim) in human plasma according to European Medicines Agency (EMA) guidelines. Protein precipitation with ice‐cold methanol containing 9 isotopically labeled internal standards was used for sample clean up. Antibiotics were detected, following a 4‐minute gradient separation, in multiple reactions monitoring (MRM) using API 4000 instrument equipped with electrospray source operating in positive ion mode. The lower limit of quantification was 0.1 mg/L for Meropenem, Ceftazidime, Piperacillin, Ampicillin, Flucloxacillin, and Sulfamethoxazole; 0.05 mg/L for Cefepime, Benzylpenicillin, and Trimethoprim; and 0.02 mg/L for Linezolid. The method proved to be precise and accurate and applicable for therapeutic drug monitoring and other pharmacokinetic studies.