Simultaneous determination of berberine in rat blood, liver and bile using microdialysis coupled to high-performance liquid chromatography

High-performance liquid chromatography coupled to microdialysis was used for the simultaneous determination of unbound berberine in rat blood, liver and bile for a pharmacokinetic study. Microdialysis probes were simultaneously inserted into the jugular vein toward the right atrium, the median lobe of the liver, and the bile duct of male Sprague–Dawley rats for biological fluid sampling after administration of berberine (10 mg/kg) through the femoral vein. Berberine and dialysates were separated using a Zorbax SB-phenyl column and a mobile phase comprised of acetonitrile–methanol–20 mM monosodium phosphate (pH 3.0) (35:20:45, v/v) together with 0.1 mM 1-octanesulfonic acid. The detection limit for berberine was 10 ng/ml. The concentration–response relationship was linear (r2>0.995) over the concentration range 0.05–50 μg/ml; intra-assay and inter-assay precision and accuracy for berberine fell within predefined limits. The disposition of berberine in the blood, liver and bile fluid suggests that berberine might be metabolized in the liver and undergo hepatobiliary excretion.