Simultaneous Determination of Four Iridoid Glycosides from Paederia Scandens in Rat Plasma by LC-MS/MS and its Application to a Pharmacokinetic Study

Background: Paederia scandens (Lour.) Merrill, belonging to the Rubiaceae family, was one of the Traditional Chinese Medicines that has been generally used to treat aches and pains, inflammation, bacillary dysentery, piles and rheumatic arthritis. The four iridoid glycosides that Paederosidic acid, Paederoside, Paederosidic acid methyl ester, and Asperuloside from Paederia scandens are considered to be the main bioactive constituents. However, their pharmacokinetics and action mechanisms of these iridoid glycosides still remain unknown. In this study, a method of simultaneous determination of four iridoid glycosides components in rat plasma with LC-MS/MS has been established and successfully applied to a pharmacokinetic study in rats, which would be favourable for further exploration. Methods: In this study, a sensitive, rapid, accurate bioanalytical method of simultaneous determination of four iridoid glycosides components from Paederia scandens extract in rat plasma with LCMS/ MS has been established. It is easy and rapid for LC-MS/MS to accurately separate and simultaneously quantify the analytes because of its high sensitivity, selectivity and accuracy. This validated method was successfully applied to a pharmacokinetic study in rats with intravenous and oral administrations of Paederia scandens extract. Results: The resulting data are fully satisfied for the selectivity and the sensitivity. Their lower limit of quantitation are in 0.25-0.5 ng/mL. Intra- and interday precisions were less than 15.0% with accuracy in the range of -15.0% to 15.0%. In the stability measurements including repeated Freeze-thaw, 4 hours at 4°C, 24 hours at 4°C, and 30 days at -80°C, the variations between the measurements and the nominated values of these compounds in plasma were detected to be less than 15.0%. The extraction recoveries of the compounds were from 85.4% to 105.6%. The bioavailability (F) of the four iridoid glycosides were 1.74% to 3.36%. Conclusion: In summary, a simple, rapid, precise, and sensitive LC-MS/MS method has been established and validated to determine the four iridoid glycosides from Paederia scandens extract in rat plasma, which was successfully applied to pharmacokinetic study in rats. The information obtained from the study will facilitate further exploration on Paederosidic acid, Paederoside, Paederosidic acid methyl ester as well as Asperuloside and these may provide valuable pharmacokinetic reference for human applications.