An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin afer oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a fow rate of 0.3 mL/min. Te detection of all compounds was accomplished by multiplereaction monitoring (MRM) in the positive electrospray ionization mode. Te LC-MS/MS method exhibited good linearity for fve analytes. Te lower limit of quantifcation (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. Te extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo afer oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. Te results demonstrated that the validated method was efciently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin afer oral administration of cortex periplocae extract.