A sensitive and high‐throughput quantitative liquid chromatography high‐resolution mass spectrometry method for therapeutic drug monitoring of 10 β‐lactam antibiotics, linezolid and two β‐lactamase inhibitors in human plasma

An ultra‐high pressure liquid chromatography high‐resolution mass spectrometric (UHPLC–HRMS) method was developed for the simultaneous and sensitive quantification of 10 β‐lactam antibiotics (cefepime, meropenem, amoxicillin, cefazolin, benzylpenicillin, ceftazidime, piperacillin, flucloxacillin, cefuroxime and aztreonam), linezolid and β‐lactamase inhibitors tazobactam and clavulanic acid in human plasma. Validation according to the EMA guidelines showed excellent within‐ and between‐run accuracy and precision (i.e. between 1.1 and 8.5%) and high sensitivity (i.e. lower limit of quantification between 0.25 and 1 mg/L). The UHPLC–HRMS method enables a short turnaround time and high sensitivity and needs only a small amount of plasma, allowing appropriate routine therapeutic drug monitoring. The short turnaround time is obtained by speeding up the protocol on multiple levels, i.e. fast and workload‐efficient sample preparation (i.e. protein precipitation and dilution), short (4 min) instrument run time, simultaneous measurement of all relevant β‐lactam antibiotics used in the intensive care unit and the use of the same instrument, column and mobile phases as for the other routine methods in our laboratory.