RAPID AND SENSITIVE DETERMINATION OF JBP485 BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY AND ITS APPLICATION IN PHARMACOKINETICS IN RAT

A sensitive high performance liquid chromatography method (HPLC) has been developed to quantify JBP485, a dipeptide with antihepatitis activity in rat biological samples. Samples of plasma and bile were analyzed following a single-step method of protein precipitation with trichloroacetic acid (10%, nu/nu). JBP485 was separated on a reversed-phase Agilent TC-C(18) column (5 mu m, 4.6 x 250 mm) at 20 degrees C. The mobile phase was comprised of methanol and water (5: 95, nu/nu). Peaks eluting from the column were detected with an ultraviolet detector at a wavelength of 203 nm. Standard curves were linear in the range 0.5-250 mu g/mL and correlation coefficients are 0.999. The intra-and inter-day precision (RSD) did not exceed 4% and 5%, respectively. Extraction recovery was better than 82.08% in blood. The method was successfully applied to investigate JBP485 plasma pharmacokinetics in rats. JBP485 appeared to have a linear pharmacokinetic characterization within doses of 6.25-100 mg/kg. The half-life is 2.32 +/- 0.16 h, plasma clearance is 2.66 +/- 0.15 mL/min/kg, volume of distribution is 0.18 +/- 0.01 l/kg and accumulated billiary excretion of JBP485 is only 2% of the total dose.