Analysis And Pharmacokinetics Study Of Coumarin Compounds In Radix Angelicae Dahuricae

Objective: 1. To establish an HPLC method for the quantification of xanthotoxol, bergapten, imperatorin and isoimperatorin in Radix Angelicae dahuricae by HPLC; To establish a liquid chromatography electrospray ionisation–tandem mass spectrometry (LC/MS/MS) method used for the investigation of the pharmacokinetics of 3 coumarin components ( imperatorin, cnidilin and isoimperatorin); and investigate the distribution of the coumarin components in mice brain.Methods: An HPLC method was used to simultaneous quantification of coumarin components in Radix Angelicae dahuricae extract. and Duliang capsules; A liquid chromatography–tandem mass spectrometry (LC/MS/MS) method was used for simultaneous determination of imperatorin, isoimperatorin and cnidilin in rat plasma. With the homogenation of brain tissue, the LC/MS/MS method was used to investigate the concentration of brain tissue and blood with respect to time as to reflect the distribution of the coumarin components in mice brain and the blood.Results: An HPLC method has been established for simultaneous quantification of coumarin components in Radix Angelicae dahuricae extract and the precision, reproducibility, The LC/MS/MS method used for the analysis of biology samples and pharmacokinetic studies of coumarin components: The method was then applied in pharmacokinetic studies of imperatorin, isoimperatorin and cnidilin in rats after oral administration of Radix Angelicae dahuricae extract. It showed that imperatorin, cnidilin and isoimperatorinin could permeate the rat blood brain barrier and show a higher distribution in brain tissue after oral administration of Radix Angelicae dahuricae extract.Conclusion: The HPLC method established in our lab proves to be simple and feasible which could be used to quantification of the courmain components in Radix Angelicae dahuricae and its formulations. The LC/MS/MS has been established to simultaneous quantification of imperatorin, cnidilin and isoimperatorin in rat plasma and its application in the pharmacokinetic studies of the 3 active courmain components after oral administration of Radix Angelicae dahuricae extract in rats. This method proved to be sensitive and specific, and precision. Imperatorin, cnidilin and isoimperatorinin could permeate the rat blood brain barrier and show a higher distribution in brain tissue after oral administration of Radix Angelicae dahuricae extract.