Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies
Date
2014
Authors
Sime, F.B.
Roberts, M.S.
Roberts, J.A.
Robertson, T.A.
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Journal article
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Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 2014; 960:134-144
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Abstract
There is strong evidence in literature supporting the benefit of monitoring plasma concentrations of -lactam antibiotics in the critically ill to ensure appropriateness of dosing. The objective of this work wasto develop a method for the simultaneous determination of total concentrations piperacillin, benzylpeni-cillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Samplepreparation involved protein precipitation with acetonitrile containing 0.1% formic acid and subsequentdilution of supernatant with 0.1% formic acid in water. Chromatographic separation was achieved ona reversed phase column (C18, 2.6 m, 2.1 × 50 mm) via gradient elution using water and acetonitrile,each containing 0.1% formic acid, as mobile phase. Tandem mass spectrometry (MSMS) analysis was per-formed, after electrospray ionization in the positive mode, with multiple reaction monitoring (MRM). Themethod is accurate with the inter-day and intra-day accuracies of quality control samples (QCs) rangingfrom 95 to 107% and 95 to 108%, respectively. It is also precise with intra-day and inter-day coefficientof variations ranging from 4 to 12% and 5 to 14%, respectively. The lower limit of quantification was0.1 g/mL for each antibiotic except flucloxacillin (0.25 g/mL). Recovery was greater than 96% for allanalytes except for ertapenem (78%). Coefficients of variation for the matrix effect were less than 10% overthe six batches of plasma. Analytes were stable over three freeze-thaw cycles, and for reasonable hours onthe bench top as well as post-preparation. This novel liquid chromatography tandem mass spectrometrymethod proved accurate, precise and applicable for therapeutic drug monitoring and pharmacokineticstudies of the selected -lactam antibiotics.
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Link to a related website: https://espace.library.uq.edu.au/view/UQ:331097/UQ331097OA.pdf, Open Access via Unpaywall
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Copyright 2014 Elsevier B.V.