Objective: To establish a UPLC-MS/MS method for simultaneous determination of ten components (oxymatrine,phellodendrine,paeoniflorin, prim-O-glucosylcimifugin, jatrorrhizine,berberine,palmatine,emodin,chrysophanol,physcion) in Zhiyang cream.Methods:The chromatographic separation was performed on an Aglient ZORBAX Eclipse Plus C18 column(2.1 mm×50 mm, 1.8 μm), with a mobile phase consisting of methanol (A)-0.1% formic acid in water (B) at the flow rate of 0.4 mL·min-1 (0-4 min, 5%A → 28%A; 4-10 min, 28%A → 30%A; 10-11 min, 30%A → 73%A; 11-16 min, 73%A → 75%A).The column temperature was 30 ℃. Electrospray ionization source (ESI), and multiple reaction monitoring (MRM), combined with positive and negative scanning switch were adopted.Results:The method has a good linearity in the range of 4.526- 452.6 μg·mL-1 (r=0.999 2) for oxymatrine, 1.625-32.50μg·mL-1 (r=0.999 0) for phellodendrine, 7.500- 150.0μg·mL-1 (r=0.998 7) for paeoniflorin,3.626-181.3 μg·mL-1 (r=0.998 9) for prim-O-glucosylcimifugin, 0.155 0-3.100 μg·mL-1 (r=0.999 3) for jatrorrhizine,3.376-168.8 μg·mL-1 (r=0.996 4) for berberine,0.015 50-15.50 μg·mL-1 (r=0.999 6) for palmatine,0.122 5-24.50 μg·mL-1 (r=0.999 8) for emodin,0.069 00-1.380 μg·mL-1 (r=0.996 8) for chrysophanol,0.016 30-0.815 0μg·mL-1 (r=0.998 9) for physcion.The average recoveries of ten active components were 96.53%-100.2% with RSDs (n=6) of less than 2.04%.The contents of oxymatrine, phellodendrine, paeoniflorin, prim-O-glucosylcimifugin, jatrorrhizine, berberine, palmatine, emodin, chrysophanol and physcion in 3 batches of samples were 2.98-3.17,0.24-0.25,1.69-1.75,0.19,0.003 6-0.004 3,0.30- 0.31,0.004 0-0.004 3,0.023-0.026,0.018-0.020 and 0.000 9-0.001 1 mg·g-1, respectively.Conclusion:The determination results of the established method may provide a basis for the quality control of Zhiyang cream.