Kinetic difference of berberine between hippocampus and plasma in rat after intravenous administration of Coptidis rhizoma extract.

In order to investigate the pharmacokinetics of berberine in Coptidis rhizoma extract in rat hippocampus and plasma, a simple and accurate high-performance liquid chromatography method was employed in this study. Berberine was determined using a Hypersil C(18) column with an isocratic mobile phase of acetonitrile-0.05 M potassium dihydrogen phosphate (containing 0.5% triethylamine, pH 3.0) and with UV detection at 236 nm. The lower limit of quantification for berberine in both hippocampus and plasma was 24 ng/ml, and the lowest concentrations of berberine determined in rat hippocampus and plasma samples were 30.7 ng/ml at 48 h and 38.5 ng/ml at 4 h, respectively. The calibration curve for berberine was linear over the concentration range 24--6000 ng/ml. At this concentration range, the overall recoveries (90.6--94.2%) for berberine were determined and the accuracy of intra- and inter-day assays from rat samples were less than 7% RSD. Following intravenous administration of C. rhizoma extract at a dose of 10.2 mg/kg containing 3 mg/kg berberine, berberine in the plasma eliminated rapidly (t(1/2 beta)=1.13 h). However, berberine in the hippocampus increased rapidly (t(1/2 alpha)=0.215 h), peaked at 3.67 h with a concentration of 272 ng/g, and had a slow elimination rate (t(1/2 beta)=12.0 h), which suggests that berberine could have a direct action on neuron and accumulate in the hippocampus. This study first showed the pharmacokinetic characteristics of berberine in rat hippocampus and the kinetic characteristics of berberine are dissimilar in the hippocampus and plasma.