Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

Sime, Fekade Bruck, Roberts, Michael S., Roberts, Jason A. and Robertson, Thomas A. (2014) Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies. Journal of Chromatography B, 960 134-144. doi:10.1016/j.jchromb.2014.04.029

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Author Sime, Fekade Bruck
Roberts, Michael S.
Roberts, Jason A.
Robertson, Thomas A.
Title Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies
Journal name Journal of Chromatography B   Check publisher's open access policy
ISSN 1570-0232
1873-376X
Publication date 2014-06-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.jchromb.2014.04.029
Open Access Status Not yet assessed
Volume 960
Start page 134
End page 144
Total pages 11
Place of publication Amsterdam, The Netherlands
Publisher Elsevier
Language eng
Abstract There is strong evidence in literature supporting the benefit of monitoring plasma concentrations of β-lactam antibiotics in the critically ill to ensure appropriateness of dosing. The objective of this work was to develop a method for the simultaneous determination of total concentrations piperacillin, benzylpenicillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 0.1% formic acid and subsequent dilution of supernatant with 0.1% formic acid in water. Chromatographic separation was achieved on a reversed phase column (C18, 2.6. μm, 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 performed, after electrospray ionization in the positive mode, with multiple reaction monitoring (MRM). The method is accurate with the inter-day and intra-day accuracies of quality control samples (QCs) ranging from 95 to 107% and 95 to 108%, respectively. It is also precise with intra-day and inter-day coefficient of variations ranging from 4 to 12% and 5 to 14%, respectively. The lower limit of quantification was 0.1. μg/mL for each antibiotic except flucloxacillin (0.25. μg/mL). Recovery was greater than 96% for all analytes except for ertapenem (78%). Coefficients of variation for the matrix effect were less than 10% over the six batches of plasma. Analytes were stable over three freeze-thaw cycles, and for reasonable hours on the bench top as well as post-preparation. This novel liquid chromatography tandem mass spectrometry method proved accurate, precise and applicable for therapeutic drug monitoring and pharmacokinetic studies of the selected β-lactam antibiotics.
Keyword Antibiotics
LC MS/MS
Pharmacokinetics
Therapeutic drug monitoring
β lactam
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1048652
APP1044941
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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