Pharmacokinetics, tissue distribution and oral bioavailability evaluation of isoimperatorin by high-performance liquid chromatography coupled with mass spectrometry

Abstract

A simple and specific high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) method was developed to investigate the plasma pharmacokinetics, tissue distribution and oral bioavailability of isoimperatorin (ISOIM), and osthole was employed as internal standard (IS). The separations were performed on a Shim-pack (VP-ODS) C18 analytical column (150 × 2.0 mm, 5 μm) with the column temperature kept at 25°C. The determinations were performed by a quadrupole mass spectrometer operated under selected ion monitoring (SIM) mode. The mobile phase was a mixture of acetonitrile and 0.5% formic acid solution (75:25, v/v) at a flow rate of 0.2 ml/min. The method was linear over the concentration range 2.0 to 5000 ng/ml (correlation coefficients >0.99). The RSDs of the overall intra- and inter-day precisions were less than 3.75%. The recoveries for ISOIM were within the range 82.70 to 97.74%. The pharmacokinetic data were successfully fitted to two-compartment models with first-order absorption. The absolute bioavailability of ISOIM is 68.17%. At 60 min after oral administration, ISOIM was found in all the seven investigated tissues. Key words: Isoimperatorin, pharmacokinetics, tissue distribution, bioavailability, high performance liquid chromatography coupled with mass spectrometry (HPLC-MS).