Pharmacokinetics and tissue distribution of 8,9-epoxy brevifolin in rats, a hepatoprotective constituent isolated from Phyllanthus simplex Retz by liquid chromatography coupled with mass spectrometry method.

8,9-Epoxy brevifolin (EBF) is a novel compound isolated from Phyllanthus siinplex Retz (P. simplex) and has been demonstrated to possess a hepatoprotective effect. The purposes of the present study were to examine the in vivo pharmacokinetics and tissue distribution of EBF in rats using a liquid chromatography coupled with mass spectrometry quantitative detection method (LC-MS/MS), with luteolin-7-0-glucoside being employed as an internal standard (IS). The method was validated within the concentration range 20-150OOng/ml, and the calibration curves were linear with correlation coefficients of >0.999. The limit of quantitation (LCQ) for EBF was 20 ng/ml. The intra-assay accuracy and precision ranged from 98.7% to 100.2% and 2.19% to 6.25%, respectively, while the inter-assay accuracy and precision ranged from 97.5% to 100.3% and 3.35% to 7.28%, respectively. The method was further applied to assess the pharmacokinetics and oral bioavailability of EBF after intravenous and oral administration in rats. The oral bioavailability of EBF was 12.46 + 2.31%. In the tissue distribution assay, its concentration was higher in the heart (13.2 + 0.24 pg/g) and liver (14.5 + 0.19 pg/g) than in other tissues. Copyright (c) 2008 John Wiley & Sons, Ltd.