Simultaneous determination of peimine and peiminine in rat plasma by LC-MS/MS and its application in the pharmacokinetic study

To establish an LC-MS/MS method for simultaneous determination of peimine and peiminine in  rat plasma after oral and intravenous administration of Fritillaria thunbergii Miq. extract, the pharmacokinetic parameters were calculated as well.  Peimine, peiminine and internal standard carbamazepine were extracted from plasma with liquid-liquid extraction by ethyl acetate, then separated on a Luna C_l8 column by using acetonitrile- water containing 10 mmol·L⁻¹ ammonium formate (35∶65), as mobile phase.  The electrospray ionization (ESI) source was applied and operated in positive ion mode.  Peimine was detected at m/z 432.4 → 414.4, peiminine at m/z 430.4 → 412.4 and carbamazepine (IS) at 237.1 → 194.2.  The linear calibration curves were obtained  at the concentration range of 0.8 − 800 ng·mL⁻¹ for peimine and peiminine.  The extraction recoveries were  94.1% − 105.3% and 85.8% − 98.6%, respectively.  The precisions, accuracy and stability of the analytes meet the requirements.  The method was shown to be effective, convenient, and suitable for simultaneous pharmacokinetic study of peimine and peiminine in rat.