Simultaneous determination of scopoletin, psoralen, bergapten, xanthotoxin, columbianetin acetate, imperatorin, osthole and isoimperatorin in rat plasma by LC–MS/MS for pharmacokinetic studies following oral administration of Radix Angelicae Pubescentis e

A rapid and sensitive bioassay based on liquid chromatography tandem mass spectrometry (LC–MS/MS) has been developed and validated for the simultaneous determination of eight coumarins in rat plasma. The liquid–liquid extraction method with ethyl acetate was used to prepare the plasma samples after addition of warfarin as an internal standard (IS). Chromatographic separation was performed on an Eclipse plus C18 column (100 mm × 4.6 mm, 1.8 μm) using gradient elution when 1 mM ammonium acetate aqueous solution – acetonitrile was used as the mobile phase. The lower limit of quantitation (LLOQ) of each coumarin was lower than 2.16 ng mL−1.Intra-day and inter-day precisions were less than 15%. The accuracies were in the range of 88.9–117%. The mean recoveries of coumarins and IS were higher than 84%. The method was successfully applied to a pharmacokinetic study of eight coumarins in rats after oral administration of radix angelicae pubescentis.

Graphical abstractMean plasma concentration versus time profiles in rats after oral administration of 6 g kg−1C Angelicae Pubescentis Radix.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► An LC–MS/MS method was developed and validated for determination of coumarins. ► The lower limits of quantitations of eight coumarins were lower than 2.16 ng mL−1. ► It was sensitive to study pharmacokinetic of Radix Angelicae Pubescentis extract. ► The main pharmacokinetic parameters of coumarins of RAP in rats were reported.