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 simplex 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‐O‐glucoside being employed as an internal standard (IS). The method was validated within the concentration range 20–15 000 ng/ml, and the calibration curves were linear with correlation coefficients of >0.999. The limit of quantitation (LOQ) 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 µg/g) and liver (14.5 ± 0.19 µg/g) than in other tissues. Copyright © 2008 John Wiley & Sons, Ltd.