Technical Abstract: A new, rapid, and reproducible reversed-phased liquid chromatographic (LC) method with mass spectroscopic detection has been developed and validated for quantification of cichoric acid, a key biomarker, in Echinacea purpurea aerial-parts based dietary supplements (EPADS). It involves the use of a short Phenomenex Hydro-RP C18 column (4 µm, 50 mm × 3.0 mm id) and a simple isocratic mobile phase profile. Selective-ion monitoring (SIM) at m/z 472.8 provided good sensitivity and a single peak chromatogram for cichoric acid despite a complex matrix. The limit of detection (LOD) is 0.03 µg/ml and the limit of quantitation (LOQ) is 0.1 µg/ml. Water/ethanol (1:1) soluble extracts of six commercially available EPADS were first profiled using a traditional HPLC/UV method. Their UV chromatograms were compared and cichoric acid was identified to be a key biomarker for EPADS. Then the samples were analyzed by the LC/MS method. The throughput increased 10 to 20 folds compared to traditional HPLC methods reported. The high-throughput method was feasible because the mass spectrometer was operated in SIM for cichoric acid only, thus eliminated interferences from other components existed in the complex matrices of the extractions of E. purpurea aerial-part preparations. The method does not require any sample clean up steps except filtration.