Pharmacokinetic Study of HRO761 in Rats by Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry

A simple and sensitive liquid chromatography tandem mass spectrometry method was established and validated for determination of HRO761 in rat plasma. After prepared by protein precipitation with acetonitrile, HRO761 and internal standard were separated on a Waters BEH C18 column using acetonitrile containing 0.1% formic acid and 0.1% formic acid in water as mobile phase by gradient elution. The method showed excellent linearity over the range of 5-5000 ng/mL with acceptable intraday and interday precision, accuracy, matrix effect, and recovery. The stability assay indicated that HRO761 was stable during the sample acquisition, preparation, and storage. The method was applied to pharmacokinetic study of HRO761 in rats. The result suggested that after intravenous administration at dose of 1 mg/kg, HRO761 was quickly eliminated from the plasma with the elimination half-life of 1.9 h. After oral administration at doses of 5, 10, and 20 mg/kg, HRO761 was quickly absorbed into plasma and reach the peak concentration (C_max) of 2598.1-9379.2 ng/mL at 1.0-4.0 h. The exposure increased proportionally with the dose. The oral bioavailability was 79.0%-99.1% over the range of 5-20 mg/kg. This study provides useful information for its further development in clinic.