Abstract: A method using UPLC-MS/MS for simultaneous determination of promethazine hydrochloride and salbutamol with automated solid phase extraction in Qingyan health food was established. Samples were extracted by ammonium acetate buffer solution and methanol, then purified by McX solid phase extraction column. The analysis was carried out on ACQUITY UPLC BEH C₁₈ (2.1 mm×50 mm, 1.7 μm) column with isocratic elution using a mobile phase making up of 0.1% aqueous formic acid (10 mmol/L ammonium formate) and methanol at 0.2 mL/min. Mass spectrometry acquisition was done in the positive ion mode and analytes were detected in the MRM mode. The pomethazine hdrochloride and salbutamol linear ranges were 4.9~49.2 and 4.3~42.7 ng·mL⁻¹, respectively. Coefficient of determination of linear regression equation of salbutamol and pomethazine hdrochloride were 0.9999 and 0.9998, respectively. Pomethazine hdrochloride and salbutamol could be separately well and had a good linear relationship. The average recovery rates of low, medium and high concentration were 87.4%~98.8%. Relative standard deviation (RSD) was 0.83%~3.9%. The detection limit of promethazine hydrochloride and salbutamol was 0.65 and 0.58 μg/kg, respectively. The developed method verified by the methodology was precise, sensitive, accurate, which therefore could be applied for the analysis in Qingyan health food.