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Abstract
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%, v/v). JBP485 was separated on a reversed-phase Agilent TC-C18 column (5 µm, 4.6 × 250 mm) at 20°C. The mobile phase was comprised of methanol and water (5:95, v/v). 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 µg/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.
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ACKNOWLEDGMENTS
The work was supported by a grant from the National Natural Science Foundation of China (No. 30672498) and the Liaoning Natural Science Fund (No. 2004225003-6). The authors would like to thank the entire staff of the Department of Clinical Pharmacology in Dalian Medical University for their kind help.