Determination and pharmacokinetic study of unbound cefoxitin in rat blood and brain with on-line microdialysis and microbore liquid chromatography Original Research Article

Simultaneous microdialysis probes were inserted into the jugular vein/right atrium and the brain striatum of male Sprague–Dawley rats to examine the unbound cefoxitin level in the rat blood and brain after cefoxitin administration (20 mg/kg, i.v.). Dialysates were directly injected to a liquid chromatographic system using an on-line injector. Samples were eluted with a mobile phase containing methanol-100 mM monosodium dihydrogen phosphate (25:75, v/v, pH 5.5). The UV detector wavelength was set at 235 nm. Using the retrograde method, the in vivo microdialytic recoveries of cefoxitin (1 and 5 μg ml−1) were 44.47±1.76 and 39.87±1.83% for the rat blood (n=6), and cefoxitin (50 and 100 ng ml−1) 16.78±3.66 and 14.56±3.13% (n=6) for the rat brain. Intra- and inter-assay accuracy and precision of the analyses were ≤11% in the range 0.05–10 μg ml−1. Pharmacokinetic analysis of results obtained using the microdialysis-chromatographic method indicated that cefoxitin penetrates the blood-brain barrier. The concentration-time plot has shown that the area under the concentration ratio of protein-unbound cefoxitin in rat brain and blood was about 3.7%.