Contents Determination And Pharmacokinetic Study Of Effective Components In Paederia Scandens

Paederia scandens(Lour.)Merrill,a climbing plant belonging to the Rubiaceae family,as a traditional Chinese medicine,has long been used for treating relevant disease of pain and inflammation.Paederosidic acid,Paederoside,Paederosidic acid methyl ester and Asperuloside,which are iridoid glycosides from Paederia scandens,are major effective components.A liquid chromatography-tandem mass spectrometer(LC–MS/MS)method for simultaneous determination of Paederosidic acid,Paederoside,Paederosidic acid methyl ester and Asperuloside in Paederia scandens Extracts and in rat plasma have been established and the latter was successfully applied to a pharmacokinetic study in rats.Details are as follows:(1)An LC-MS/MS method for simultaneous determination of Paederosidic acid,Paederoside,Paederosidic acid methyl ester and Asperuloside in Paederia scandens Extracts has been established and validated by relative methodology.The contents of Paederosidic acid,Paederoside,Paederosidic acid methyl ester and Asperuloside in Paederia scandens Extracts are 87.4 mg/g,24.2 mg/g,20.3 mg/g,3.2 mg/g,respectively.(2)Simultaneous determination of four iridoid glycosides components from Paederia scandens extract in rat plasma with LC–MS/MS has been established.Selectivity,linear range,precision,accuracy,stability,recovery and matrix effect were performed for establishment and validation of methodology,and the results showed that the analysis method is selective and sensitive.The LLOQ are 0.25-0.5 ng/mL for the four iridoid glycosides.Inter-/intro precision and accuracy,stability conforms to the requirements of the relevant quantitative analysis of biological samples,with the average recovery is between 85.4% and 105.6%.The method is suitable for the simultaneous determination of four iridoid glycosides from Paederia scandens in rat plasma of pharmacokinetic study.(3)The concentrations of the four iridoid glycosides in rat plasma were simultaneously determined with the validated LC–MS/MS method after that the rats were administrated Paederia scandens extracts and the pharmacokinetic characteristics in rats of the four iridoid compounds were studied by single dose intravenous administration(50 mg/kg)and a single dose oral administration(3 g/kg).Results showed that absorbtion of Paederoside,Paederosidic acid methyl ester and Asperuloside were rapid by gastric gavage of 3 g/kg Paederia scandens extracts in rats,whose Tmax were between 0.29 and 0.33 h;while the absorbtion of Paederosidic acid were comparatively slow with Tmax 1.69 h.Half-life T1/2 of the four iridoid compounds were between 2.47 h and 4.22 h.The half-life T1/2 of the four iridoid glycosides in rat plasma after intravenous administration of Paederia scandens extracts were 1.21-3.16 h.The bioavailability of Paederoside,Paederosidic acid methyl ester and Asperuloside when rats were orally adnimitrated Paederia scandens extracts were poor,3.36 ± 1.14%,2.00 ± 0.62%,1.84 ± 0.60%,1.74 ± 0.50%,respectively.There are more understanding for pharmacokinetic characteristics of Paederoside,Paederosidic acid methyl ester and Asperuloside from Paederia scandens in rats by the study,which could provide reference and guidance for clinical administration and as the basis for further research and development.