Pharmacokinetic UPLC–MS/MS studies on byakangelicol after oral and intravenous administration to rats

Abstract

Byakangelicol is one of coumarins from Baizhi and has been shown to inhibit the release of PGE2 from human lung epithelial A549 cells in a dose-dependent manner. A sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and full validated for the quantification of byakangelicol in rat plasma. The pharmacokinetics of byakangelicol after both intravenous (5 mg/kg) and oral (15 mg/kg) administrations were studied. Chromatographic separation was performed on an ultra-performance liquid chromatography ethylene bridged hybrid (UPLC BEH) C18 column with acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min; fargesin was used as the internal standard (IS). The following quantitative analysis of byakangelicol was utilized in the multiple reaction monitoring mode. The samples were extracted from rat plasma via protein precipitation using acetonitrile. In the concentration range of 1–2000 ng/mL, the method correlated linearity (r > 0.995) with a lower limit of quantitation (LLOQ) of 1 ng/mL. Intra-day precision was less than 11%, and inter-day precision was less than 12%. The accuracy was between 92.0% and 108.7%, the recovery was better than 89.6%, and the matrix effect was between 85.9% and 98.6%. The method was successfully applied to a pharmacokinetic study of byakangelicol after intravenous and oral administration, and the absolute bioavailability was 3.6%.