Objective: To develop a simple

rapid and accurate HPLC-MS/MS for the determination of sinomenine in human plasma and study on pharmacokinetics of sinomenine after oral administration of Qishe pills. Method: Human plasma samples were prepared by protein precipitation method with methanol as solvent.The separation of sinomenine and propranolol (the internal standard

IS) was performed on a ZORBAX SB-C18 column with mobile phase of methanol-water (containing 0.1% formic acid and 5 mmol·L-1 ammonium formate) for gradient elution.Electrospray ionization (ESI) mass spectrometry was operated in the positive ion mode with selected reaction monitoring (SRM) of the transitions at m/z 330.2-152.2 for sinomenine and m/z 260.2-183.1 for IS.Pharmacokinetic parameters were calculated by WinNonlin 6.3 software. Result: The linear range of sinomenine in human plasma was 5-1 000 μg·L-1 with the lower limit of quantitation (LLOQ) of 5.0 μg·L-1

the relative standard deviations of intra-batch and inter-batch precision were below 15.0%

while the deviations of assay accuracy were within ±10.0%.The extraction recovery of sinomenine was 103.3% and no obvious matrix effect was observed.The main pharmacokinetic parameters of sinomenine (Tmax

Cmax

AUC0-48 h and t1/2) after oral administration of Qishe pills were (2.5±0.8) h

(477.9±60.1) μg·L-1

(4 808.8±791.7) h·μg·L-1 and (7.5±1.3) h

respectively. Conclusion: The validated method is successfully applied to pharmacokinetics of sinomenine in human after oral administration of Qishe pills

which can provide a methodological basis and data for the future clinical studies of this preparation.