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

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 beta-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 beta-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 beta-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 beta expectation tolerance intervals. The acceptance limits were settled at +/- 30% according to the regulatory requirements. Assay validation demonstrated good performance for all beta-lactams analyzed in terms of trueness, repeatability, linearity and intermediate precision over the range of 2-200 mu g/mL. The simple extraction procedure provides respective absolute and relative recoveries ranging from 70% to 86% and from 66% to 89% for all the beta-lactams analyzed. Few interferences were observed and the method was easily applicable to TDM in intensive care patients. The quantification of beta-lactams should allow for antibiotic regimen adjustment in critically ill patients. (C) 2012 Elsevier B.V. All rights reserved.