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

Biomed Chromatogr. 2021 Feb 16:e5092. doi: 10.1002/bmc.5092. Online ahead of print.


An ultra-high pressure liquid chromatography high resolution mass spectrometric (UHPLC-HRMS) method was developed for the simultaneous and sensitive quantification of ten beta-lactam antibiotics (cefepime, meropenem, amoxicillin, cefazolin, benzylpenicillin, ceftazidime, piperacillin, flucloxacillin, cefuroxime and aztreonam), linezolid and beta-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 (LLOQ) between 0.25 to 1 mg/L). The UHPLC-HRMS method enables a short turnaround time, high sensitivity and needs only a small amount of plasma, allowing appropriate routine TDM. 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 beta-lactam antibiotics used in the intensive care unit and the use of the same instrument, column and mobile phases as the other routine methods in our laboratory.

PMID:33590498 | DOI:10.1002/bmc.5092