Background and Importance Linezolid is an oxazolidinone antibiotic with time-dependent activity and moderate post-antibiotic effect used as a treatment against multidrug-resistant gram-positive pathogens. Recent guidelines recommend therapeutic drug monitoring (TDM) of linezolid in critically ill patients, who often manifest great inter- and intra-individual pharmacokinetic variability. The latter is the reason why in this kind of patients conventional dosing may not achieve optimal efficacy and safety concentrations (2–7 mcg/mL).
Aim and Objectives The aim of this study was the development and validation of a high-performance liquid chromatography (HPLC) method for measuring linezolid in human plasma using tedizolid as an internal standard (IS).
Material and Methods The chromatographic system consisted of an Agilent® 1260 Infinity with an ultraviolet diode array detector (UV-DAD). The column used was a BDS HYPERSIL C18 4.6X250 mm, 5 µm (Thermo Scientific®, USA). The method was developed under isocratic conditions and the analysis run time was 8 minutes. The method was validated according to the Food and Drug Administration (FDA) bioanalytical method validation guidance. Chromatographics conditions and calibration methods are shown in table 1. Plasma drug extraction was performed by adding 100 µL of IS (tedizolid 25 µg/mL) into a test tube, followed by 250 µL of plasma (QC or samples) and 500 µL of acetonitrile/methanol (50/50, v/v). The tube was vortexed for 1 min and then centrifuged at 15000 rpm for 5 min. After centrifugation, 300 µL of the supernatant was injected into the HPLC.
Conclusion and Relevance A method has been validated for the determination of linezolid by HPLC in human plasma. This will allow in future to improve therapeutic outcomes in critically ill adult patients, limiting the risk of dose-related adverse effects and avoiding suboptimal concentrations.
Conflict of Interest No conflict of interest
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