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 microg/g) and liver (14.5 +/- 0.19 microg/g) than in other tissues.
Niu
Xiaofeng
X
Faculty of Pharmacy, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China. Pharmniuxf@hotmail.com <Pharmniuxf@hotmail.com>
Li
Weifeng
W
He
Langchong
L
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D008297:Male; D029803:Phyllanthus; D010865:Pilot Projects; D020011:Protective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*; D014018:Tissue Distribution
C523498:8,9-single-epoxy brevifolin; D020011:Protective Agents; D043823:Taxoids