A comprehensive analytical method based on ultra fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for the simultaneous determination of phenylethanoid glycosides,lignans,flavonoids and phenolic acids in Forsythiae Fructus.Conditions for the herbs extraction were optimized by the response surface method(RSM).Subsequently,the extract was separated on an XBridge-C18 column(4.6 mm×100 mm,3.5 μm) by gradient elution with 0.1% aqueous formic acid solution-acetonitrile as mobile phase at a flow rate of 0.8 mL/min at 30 ℃,and analyzed under multiple reaction monitoring(MRM) mode.Results showed that,the optimum sample extraction conditions were as follows:72% of methanol volume fraction,38∶1 mL/g of liquid to material ratio and 60 min of extraction time.Additionally,the 21 analytes showed good linearities in corresponding concentration ranges with their correlation coefficients(r) no less than 0.999 0.The limits of detection and the limits of quantitation were 0.001-233.710 ng/mL and 0.002-771.250 ng/mL,respectively.The precision,repeatability and stability of the method were all satisfactory.Average spiked recoveries ranged from 98.6% to 102% with relative standard deviations(RSD) between 0.89% and 3.8%.The method developed is accurate and reliable,and provides a new reference for the quality evaluation and control of Forsythiae Fructus.