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

Simultaneous microdialysis probes were inserted into the jugular vein/right atrium and the brain striatum of male Sprague-Dawley rats to examine the u nbound cefoxitin level in the rat blood and brain after cefoxitin administr ation (20mg/kg, i.v.). Dialysates were directly injected to a liquid chroma tographic system using an on-line injector. Samples were eluted with a mobi le 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 retr ograde method, the in vivo microdialytic recoveries of cefoxitin (1 and 5 m u g ml(-1)) were 44.47+/-1.76 and 39.87+/-1.83% for the rat blood (n=6), an d 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 analys es were less than or equal to 11% in the range 0.05-10 mu g ml(-1). Pharmac okinetic analysis of results obtained using the microdialysis-chromatograph ic method indicated that cefoxitin penetrates the blood-brain barrier. The concentration-time plot has shown that the area under the concentration rat io of protein-unbound cefoxitin in rat brain and blood was about 3.7%. (C) 2000 Elsevier Science B.V. All rights reserved.