On-line microdialysis coupled with microbore liquid chromatography with ultraviolet detection for continuous monitoring of free cefsulodin in rat blood

A microdialysis method followed by a microbore liquid chromatographic ultra violet detection procedure has been performed for the assay of unbound cefs ulodin in rat blood. A microdialysis probe was inserted into the jugular ve in for blood sampling. This method involves an on-line design for submittin g dialysate into the liquid chromatographic system. The chromatographic con ditions consisted of a mobile phase of methanol-100 mM monosodium phosphori c acid (10.90, v/v, pH 5.0) pumped through a microbore reversed-phase colum n at a flow-rate of 0.05 ml/min. Detection wavelength was set at 265 nm. Mi crodialysis probes, being laboratory-made, were screened for acceptable in vivo recovery while chromatographic resolution and detection were validated for response linearity as well as intra- and inter-day variabilities. The method was then applied to pharmacokinetics profiling of cefsulodin in the blood following intravenous administration of cefsulodin (20 mg/kg) in rats . Pharmacokinetics were calculated from the corrected data for dialysate co ncentrations of cefsulodin versus time. Based on pharmacokinetic calculatio n, cefsulodin best fitted to a two-exponential disposition. This study prov ided specific pharmacokinetic information for protein-unbound cefsulodin an d demonstrated the applicability of this continuous sampling method for pha rmacokinetic study. (C) 2001 Elsevier Science B.V. All rights reserved.