Around 20 % of adults experience chronic pain which is associated with considerable individual suffering and with significant costs to society.Neuropathic pain resulting from injury to the central and peripheral nervous system is one of the main causes of chronic pain.Chinese herbal medicine has a long tradition in treating neuropathic pain.Sinomenine is an aLkaloid and a morphinan derivative isolated from the root of Sinomenius acutum (in China known as Qing-teng).Some research have found sinomenine has a significant effect in the treatment of neuropathic pain.A specified and sensitive method to investigate the pharmacokinetic characteristics of sinomenine which is more close to clinical is needed.Objective: To establish a HPLC-MS/MS method for determining sinomenine in rat plasma and to investigate the pharmacokinetic characteristics of sinomenine in rats.Method: SD rats were jugular vein cannula and intrapcritoneal injected with 40 mg·kg-1 sinomeninc the next day, their blood samples were collected in conscious and active rats at different time points by automatic blood sampler.The plasma concentration of sinomenine was determined by HPLC-MS/MS, and the pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.2 software.Result: The regression equation of sinomeninc in rats plasma was Y=1.3547 X+0.0934 (rz=0.9986), which showed a good linear relation at 7.5-969.5 mg·L-1.The method showed a recovery of more than 85%, and both inter-day and intra-day RSDs were less than 15%.After ntraperitoneal injected with 40 mg·kg-1 sinomenine, the main pharmacokinetics parameters of Tmax, Cmax, AUClast, Vz/F, CL/F, MRTlast were respectively 0.5 h, 346.9 mg.L-1, 1494.2h.mg·L-1, 248.4 L·kg-1, 25.3 L.h-1·kg-1, 5.2 h.Conclusion: It is first time to establish such a method using automatic blood sampler and HPLC-MS/MS to collect blood sample and determine the concentration of sinomcnine in plasma.The method is so highly specified and sensitive that it can be used in quantitative analysis in vivo on sinomenine.