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Abstract
Pharmacokinetic/pharmacodynamic indices of anti-infective drugs should be referenced to free drug concentrations. In the present study, clindamycin, flucloxacillin and tedizolid have been determined in human plasma by HPLC-UV. The drugs were separated isocratically within 3-6 min on a C18 column using mixtures of phosphate buffer-acetonitrile of pH 7.1-7.2. Sample treatment for the determination of total drug concentrations in plasma included extraction/back-extraction (clindamycin) or protein precipitation (flucloxacillin, tedizolid). The free drug concentrations were determined after ultrafiltration. An ultrafiltration device with a membrane consisting of regenerated cellulose proved to be suitable for all drugs. Maintaining a physiological pH was crucial for clindamycin, whereas maintaining body temperature was essential for tedizolid. The methods were applied to the analysis of total and free drug concentrations in clinical samples and were sufficiently sensitive for pharmacokinetic studies and therapeutic drug monitoring.
Highlights
Clindamycin (CLI) is a lincosamide antibiotic with similar mechanism of action to macrolides, e.g. clarithromycin
Regarding the determination of free concentrations in clinical samples, spiked plasma samples were included as quality controls (QC) in each run of unknown samples to assess inter-assay precision
Clindamycin and TZD were determined in serial plasma samples from healthy volunteers after short infusion of CLI phosphate equivalent to 900 mg CLI or 200 mg TZD phosphate
Summary
Clindamycin (CLI) is a lincosamide antibiotic with similar mechanism of action to macrolides, e.g. clarithromycin. The importance of developing accurate, fast and affordable bioanalytical methods for measuring free drug concentrations has been emphasized recently (Musteata, 2017) Ultrafiltration fulfils these requirements, but the type of membrane, temperature, pH and relative centrifugal force can significantly influence the results (Nilsson, 2013). The aim of the present study was to establish HPLC–UV methods for the determination of CLI, FXN and TZD in human plasma with focus on the determination of the free, pharmacologically active drug. Vivafree 500 30 K centrifugal filters, which are identical to Vivacon 500 30 K (Sartorius, Göttingen, Germany), but manufactured as CE-registered in vitro diagnostic medical devices, and recommended for the determination of free drug in plasma, were obtained from Vivaproducts Inc. Sample treatment for the determination of the free plasma concentrations was performed by ultrafiltration as previously described (Kratzer, Liebchen, Schleibinger, Kees, & Kees, 2014).
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