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

摘要

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 trichlor-oacetic acid (1CP/o, v/v). JBP485 was separated on a reversed-phase Agilent TC-Cjs column (5mum, 4.6x 250mm) at 2CPC. The mobile phase was comprised of methanol and water (5:95, v/v). Peaks elutingfrom the column were detected with an ultraviolet detector at a wavelength of 203nm. Standard curves were linear in the range 0.5-250 mug/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 82.08Vo in blood. The method was successfully applied to investigate JBP485 plasma pharmacokinetics in rats. fBP485 appeared to have a linear pharmacoki-netic characterization within doses of 6.25-100mgjkg. The half-life is 2.32+-0.16h, plasma clearance is 2.66+-0.15mL/min/kg, volume of distribution is 0.18+-0.011/kg and accumulated billiary excretion of JBP485 is only 2% of the total dose.