Simultaneous blood and brain sampling of cephalexin in the rat by microdialysis and microbore liquid chromatography: application to pharmacokinetics studies

To circumvent the need for laborious sample clean-up and multiple blood sam pling, a system was developed consisting of on-line microdialysis coupled t o microbore liquid chromatography and ultraviolet detection. The system was designed for the simultaneous and continuous monitoring of unbound blood a nd brain cephalexin in the rat following single bolus intravenous administr ations (10 mg/kg, n=6). Microdialysis probes were inserted into the jugular vein and brain striatum, respectively, for blood and brain sampling. Chrom atographic conditions consisted of a mobile phase of methanol-100 mM monoso dium phosphoric acid (20:80, v/v, pH 5.0) pumped through a microbore revers ed-phase column at a flow-rate of 0.05 ml/min. Detection wavelength was set at 260 nm. The method was validated for response Linearity as well as intr a- and inter-day variabilities. Rapid appearance of cephalexin in the stria tal dialysate suggested good blood-brain barrier penetration. This study pr ovided pharmacokinetics information for cephalexin as well as demonstrated the applicability of this continuous sampling method for pharmacokinetics s tudies. (C) 2000 Elsevier Science B.V. All rights reserved.