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Therapeutic drug monitoring of linezolid: HPLC-based assays for routine quantification of linezolid in human serum and cerebrospinal fluid

Abstract

Objective Therapeutic drug monitoring (TDM) of linezolid can prevent over- and under-dosing in critically ill patients and can be crucial to successful antibiotic treatment. Quick and simple high-performance liquid chromatography (HPLC) assays for the detection of linezolid in human serum and cerebrospinal fluid (CSF) were developed in this study.

Methods The methods used an Atlantis T3 5.0 µm stationary phase. The mobile phase A contained water (99.4% m/m) and formic acid (0.6% m/m) (pH 2.30). The mobile phase B contained acetonitrile (93.6% m/m), water (6% m/m) and formic acid (0.4% m/m). The methods were isocratic, using 23% of mobile phase B and 77% of mobile phase A. Ultraviolet absorbance detection at 252 nm was used. For sample preparation an internal standard was added, and acetonitrile/methanol was added for protein precipitation.

Results The methods were investigated for linearity, specificity, accuracy, and precision. Stability of linezolid and internal standard was assessed. The retention times of linezolid were 8.5 min and 8.1 min, and the single run time was 15 min. Linezolid was quantified from the lower limit of quantification (0.2 mg/L) to the upper limit of quantification (50 mg/L, 75 mg/L, and 100 mg/L). In routine analysis a high variability of serum and CSF levels was observed and the mean CSF/serum ratio was 0.71±0.16.

Conclusion The developed assays enable the study of correlations between the applied dosage, serum concentration and CSF concentration. Additionally, studies with a higher number of samples can be performed to investigate the penetration of linezolid into the central nervous system.

  • therapeutic drug monitoring
  • critical care
  • clinical medicine
  • drug monitoring
  • microbiology

Data availability statement

No data are available. Not applicable.

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