OBJECTIVE: To establish a method for the separation and detection of related substances in baicalein, identify its structure and preliminarily explore the degradation mechanism. METHODS: HPLC was adopted to detect the baicalein, related impurities and forced destruction of degradation products in synthesis process: the column was ES Industries® FluoroSep-RP Phenyl with mobile phase of 0.3% formic acid-methanol-acetonitrile (gradient elution) at a flow rate of 1.0 mL/min, the detection wavelength was 275 nm, the column temperature was 10 ℃,and the injection volume was 10 μL. LC-MS/MS was conducted to identify the related substances and conjecture degradation mechanism: the column was ES Industries® FluoroSep-RP Phenyl with mobile phase of 0.3% formic acid - methanol (gradient elution) at a flow rate of 1.0 mL/min, the detection wavelength was 275 nm, column temperature was 10 ℃, and the injection volume was 10 μL; ion source was electrospray ion source, positive and negative ions, nebulizer pressure was 55 psi and the drying gas flow was 11 L/min, drying gas temperature was 350 ℃, capillary voltage was 4.0 kV, detection modes were full-scan first-order MS and selective ion full-scan second-order MS, scan ranges were m/z 100-1 000 (first-order MS) and 50-500 (second-order MS), ionization voltage was 80-135 eV, and the collision energy was 10-30 eV. RESULTS: The linear range of baicalein was 2.4-480 μg/mL(r=0.999 9); RSDs of precision, stability and reproducibility tests were lower than 2.0%; the limit of quantitation was 7.2 ng,the limit of detection was 2.4 ng. Baicalein was well separated with related substance and 3 major degradation products, the related substance was chemical synthesis precursor wood butterfly; the degradation products were 6, 7-quinone derivatives and 7, 8-quinone derivatives, which were isomers; oxidative degradation products were benzoic acid phenyl ester derivatives. CONCLUSIONS: The main mechanisms of alkali degradation and oxidative degradation of baicalein include pyran, reciprocal rearrangement and oxidation reaction; the established method is specific and sensitive, and can be used for the detection of related substances in baicalein.