A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection

Briscoe, Scott E., McWhinney, Brett C., Lipman, Jeffrey, Roberts, Jason A. and Ungerer, Jacobus P. J. (2012) A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 907 178-184.


Author Briscoe, Scott E.
McWhinney, Brett C.
Lipman, Jeffrey
Roberts, Jason A.
Ungerer, Jacobus P. J.
Title A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection
Journal name Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences   Check publisher's open access policy
ISSN 1570-0232
1873-376X
Publication date 2012-10-15
Sub-type Article (original research)
DOI 10.1016/j.jchromb.2012.09.016
Volume 907
Start page 178
End page 184
Total pages 7
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2013
Language eng
Abstract With the clinical imperative to further research in the area of optimising antibiotic dosing in the intensive care setting, a simple high performance liquid chromatography method was developed and validated for routinely determining the free (unbound) concentration of ten beta-lactam antibiotics in 200 μL of human plasma. Antibiotics determined include three cephalosporins (ceftriaxone, cephazolin and cephalotin); two carbapenems (meropenem and ertapenem); and five penicillins (ampicillin, piperacillin, benzylpenicillin, flucloxacillin and dicloxacillin). There was a single common sample preparation method involving ultracentrifugation and stabilisation. Chromatography was performed on a Waters XBridge C18 column with, depending on analytes, one of four acetonitrile-phosphate buffered mobile phases. Peaks of interest were detected via ultraviolet absorbance at 210, 260 and 304 nm. The method has been validated and used in a pathology laboratory for therapeutic drug monitoring in critically ill patients. The significant variability in the level of protein binding that is common with antibiotics traditionally considered to have high protein binding (e.g. ceftriaxone, cephazolin, ertapenem, flucloxacillin and dicloxacillin) suggests that this assay should be preferred for measuring the pharmacologically active concentration of beta-lactam antibiotics in a therapeutic drug monitoring programme.
Keyword Free
Unbound
Beta-lactam
Antibiotics
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published under Short communication

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
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