Quantitative determination of unbound cefoperazone in rat bile using microdialysis and liquid chromatography

Cefoperazone is a third generation cephalosporin antibiotic with a broad spectrum against gram-positive and gram-negative bacteria. It is clinically effective in the treatment of the biliary tract infections. In the present study, we utilized microdialysis sampling technique with shunt linear probe for continuous monitoring levels of cefoperazone from rat biliary ducts. The effects of berberine (a potential P-glycoprotein enhancer) pretreatment were also evaluated. Analysis of cefoperazone in the dialysates was achieved using a reversed phase RP-18 column (250 mm x 4.6 mm i.d.; particle size 5 microm) maintained at ambient temperature. The mobile phase comprised 100 mM monosodium phosphate (pH 5.5)-methanol (70:30, v/v), and the flow rate of the mobile phase was 1 ml/min. The UV detector wavelength was set at 254 nm. The area under the concentration-time curve and elimination half-life of cefoperazone were about 242.3+/-13.4 min mg/ml and 64.1+/-28.2 min, respectively. No significant effect was showed on the pharmacokinetics of cefoperazone with berberine pretreatment. This study represents a successful application of biliary microdialysis sampling technique, which is feasible for pharmacokinetic and biliary drug excretion studies.