Rapid quantification of six β-lactams to optimize dosage regimens in severely septic patients

Abstract

A fast analytical procedure was developed for the simultaneous quantification of cefepime (CEF), meropenem (MEM), ceftazidime (CZA), cefuroxime (CFX), aztreonam (AZT), and piperacillin (PIP) in serum of intensive care patients. The β-lactam pharmacokinetic parameters can be altered in severe sepsis due to changes in the distribution, the metabolism and the elimination process. Therapeutic drug monitoring (TDM) of β-lactams is therefore recommended in critically ill patients. The plasma samples were spiked with cefoperazone as internal standard and proteins were precipitated with methanol. The different β-lactams were separated with high performance liquid chromatography within 18 min, and quantified by UV spectrophotometry with a diode array detector. The method was validated by means of the accuracy profile approach based on β expectation tolerance intervals. The acceptance limits were settled at ± 30% according to the regulatory requirements. Assay validation demonstrated good performance for all β-lactams analyzed in terms of trueness, repeatability, linearity and intermediate precision over the range of 2-200 μg/mL. The simple extraction procedure provides respective absolute and relative recoveries ranging from 70% to 86% and from 66% to 89% for all the β-lactams analyzed. Few interferences were observed and the method was easily applicable to TDM in intensive care patients. The quantification of β-lactams should allow for antibiotic regimen adjustment in critically ill patients.