Abstract: OBJECTIVE To develop a method for simultaneous determination of piperine, piperlonguminine, corilagin, gallic acid, ellagic acid, quercetin, rutin in Mongolian medicine Sanzhiqing by HPLC-MS/MS, and to optimize the ethanol extraction technology. METHODS The separation was performed on Shim-pack GIST-HP C₁₈ column(2.1 mm×100 mm, 3 μm), mobile phase consisting of water(containing 0.1% formic acid) and methanol with gradient elution at a flow rate of 0.25 mL·min^-1, and the injection volume was 2 μL. Multiple-reaction monitoring was employed with switching electrospray ion source polarity in positive and negative mode. With comprehensive score of the content of 7 ingredients as the inspection index and material-liquid ratio, ethanol concentration, extraction time and extraction times as the inspection factor, the L₉(3⁴) orthogonal test design was used to optimize the ethanol extraction technology of Sanzhiqing. RESULTS There was a good linear relationship between the peak area and the mass concentration of the 7 components in Sanzhiqing(r ≥ 0.999 1). The RSD of instrument precision, repeatability and stability were all <5%, and the average recoveries ranged from 99.54% to 105.32% and the RSD ranged from 1.39% to 4.33%. The optimal ethanol extraction technology included solid-liquid ratio of 1:8, ethanol concentration of 40%, extracting for 0.5 h and extracting for 3 times. Results of three validation tests showed that average content of the above 7 ingredients was 9.852, 0.587, 16.247, 3.657, 8.663, 0.119, 0.104 mg·g^-1 respectively. CONCLUSION The established method is simple, sensitive and efficient, and can be used for determine the content of various main active ingredients in Sanzhiqing, and the optimized ethanol extraction technology is stable and feasible.