High-performance liquid chromatography assay for moxifloxacin in brain tissue and plasma: Validation in a pharmacokinetic study in a murine model of cerebral listeriosis

摘要

Moxifloxacin is a broad-spectrum antibacterial 8-methoxy-fluoroquinolone. In order to evaluate the pharmacokinetic properties of moxifloxacin in mouse plasma and brain tissue, we developed a high-performance liquid chromatography (HPLC) method. This study was based on single-drug delivery, intravenously dosed in a central listeriosis murine model. The method employed a reversed-phase Lichrospher RP-18 with a precolumn (250 4.6 mm) and a mobile phase composed of a mixture of acetonitrile, methanol, and citric buffer (pH = 3.5) with sodium dodecyl sulfate and tetrabutylammonium bromide. Fluorescence detection was performed at an excitation wavelength of 290nm and an emission wavelength of 550nm. The relative standard deviation of intra- and inter-day assays was 10. This validated method led to a short retention time (8.0min) for moxifloxacin. The standard curves were linear from 5250g/L in plasma and from 0.12.5g/g of brain tissue. The limits of quantification were 5g/L in plasma and 0.1g/g in brain tissue. The method enabled the detection of systemic antimicrobial in plasma and in CNS in Listeria-infected mice. Injected moxifloxacin passed through the encephalic barrier within a 30 to 60 min after injection time frame. Moxifloxacin pharmacokinetics are modeled in an infected model compared to control mice.