An HPLC-MS/MS method for the quantitative determination of platycodin D in rat plasma and its application to the pharmacokinetics of Platycodi Radix extract

AIMS:To develop an HPLC-MS/MS method for the quantification of platycodin D(PD) in rat plasma,and to acquire the main pharmacokinetic parameters of PD after oral administration of pure PD or of Platycodi Radix extract(PRE) containing PD.METHOD:Plasma samples were pretreated with solid-phase extraction using an Oasis HLB SPE cartridge.Madecassoside was used as the internal standard(IS).Chromatographic separation was achieved on an ODS column(100 mm2.1 mm i.d.,3.5 m) with a mobile phase consisting of acetonitrile/water(30:70,V/V) containing 0.1 mmolL-1 ammonium acetate at a flow rate of 0.25 mLmin-1.The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization(ESI) source with a chromatographic run time of 3.0 min.The detection was operated by multiple reaction monitoring(MRM) of the transitions of m/z 1 223.6469.2 for PD and of m/z 973.6469.2 for madecassoside(IS),respectively.RESULTS:The calibration curve was linear from 5 to 2 000 ngmL-1(r20.99) with a lower limit of quantification(LLOQ) of 5 ngmL-1.The intra-and inter-day precision(relative standard deviation,RSD) values were below 15% and the accuracy(relative error,RE) was from-15% to +15% at three quality control(QC) levels.Plasma concentrations of PD were determined for 24 h after i.v.administration of PD,and oral administration of PD and PRE,respectively.The absolute oral bioavailability of PD in rats was found to be(0.480.19)% when administered PD,and to be(1.810.89)% when administered PRE.CONCLUSION:The developed HPLC-MS/MS method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of PD in rats after administration of PD and Platycodi Radix extract.