Abstract: The method mentioned by the title was proposed after optimizing amounts of purification agent and extraction solvent by single factor and response surface methodology. The 2 g of crushed puffed food sample was taken, and 10 mL of water, 10 mL of acetonitrile, 4 g of anhydrous magnesium sulfate and 1 g of sodium chloride were added in sequence. The mixture was vortexed for 15 min and centrifuged for 5 min, and 2 mL of supernatant was taken and placed into a centrifuge tube containing 200 mg of octadecylsilane bonded silica gel (C₁₈) and 30 mg of N-propylethylenediamine (PSA). After vortexing for 2 min, and centrifuging for 5 min, the supernatant was passed through a 0.22 μm filter membrane, and the filtrate was determined by ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Cannabidiol, cannabinol and tetrahydrocannabinol in the filtrate were separated by gradient elution with mixed solutions of 0.1% (volume fraction) aqueous ammonia solution and acetonitrile at different volume ratios on the Agilent Extend C₁₈ chromatographic column, ionized by negative ion mode of electrospray ion source, and quantified by matrix matching method. It was shown that the established three-factor three-level response surface model was a quadratic regression equation with correlation coefficient of 0.994 9. Under the optimal conditions (C₁₈, PSA, and acetonitrile amounts of 200 mg, 30 mg, and 10 mL, respectively), the experimental value (94.1%) and predicted value (93.6%) of the tetrahydrocannabinol recovery were consistent. Linear relationships between values of the mass concentrations of the 3 targets and peak areas of the corresponding parent ions were kept in the range of 5.0-200 μg·L⁻¹, with the same detection limit (3S/N) of 10.0 μg·kg⁻¹. Test for the spiked recovery at the 3 concentration levels was conducted on negative rice cakes, giving recoveries in the range of 81.9%-94.1%, and RSDs (n=6) of the determined values ranged from 3.9% to 7.3%. The proposed method was used for the analysis of samples of rice cakes, biscuits, and potato chips samples. Cannabinol (27.8 μg·kg⁻¹), cannabidiol (113 μg·kg⁻¹) and tetrahydrocannabinol (30.6 μg·kg⁻¹) were detected in one imported biscuit sample, while these 3 targets were not detected in the other samples.