Validated High-performance Liquid Chromatography Method for the Determination of JW5624, A New Class Of Hepatitis C Virus Inhibitor, in Rat Plasma and its Application in the Pharmacokinetic Study of JW5624.

Abstract

We developed unique small-molecule inhibitors of hepatitis C virus (HCV), which had potent activity for HCV entry inhibition and multi-genotypic antiviral activity. In this study, a sensitive and reliable method for the quantitation of JW5624 in rat plasma was developed and validated using high performance liquid chromatography. Chromatographic separation was achieved using a reversed-phase (C18) column. The mobile phase, 0.02 M ammonium acetate buffer:acetonitrile (30:70, v/v), was run at a flow rate of 1.0 mL/min, and the column eluent was monitored using an ultraviolet detector at 254 nm at room temperature. The retention times of sildenafil (an internal standard), and JW5624 were approximately 5.9 and 7.3 min, respectively. The detection limit of JW5624 in rat plasma was 0.03 μg/mL. Pharmacokinetic parameters of JW5624 was evaluated after intravenous (i. v.; at doses of 5 mg/kg) and oral (p.o.; at doses of 10 mg/kg) administration of JW5624 in rats. After p.o. administration (10 mg/kg) of JW5624, F value was approximately 71.0%. These results suggest that JW5624 can be a potential candidate drug for the development of HCV entry inhibitors.