Abstract: OBJECTIVE To establish a method for the quantitative determination of 4 alkaloids in compound glycyrrhiza oral solution by UPLC-MS/MS. METHODS Chromatography was carried on a Waters BEH C₁₈ column(50 mm×2.1 mm, 1.7 μm) with the mobile phase consisting of 0.02 mol·L^-1 ammonium acetate water solution(containing 0.1% formic acid)(A) and methanol(B) in a programme of gradient elution(0-1.5 min, 92%A; 1.5-2.0 min, 92%A→60%A; 2.0-4.5 min, 60%A; 4.5-4.6 min, 60%A→92%A; 4.6-5.0 min, 92%A). The flow rate was 0.2 mL·min^-1 with a column temperature at 35 ℃. Determination was performed by multiple reaction monitoring mode using electrospray ionization in positive ion mode. RESULTS The linear ranges of morphine, codeine, papaverine and cocaine were 5.68-113.4, 1.04-20.85, 0.53-10.58 and 0.16-3.13 μg·L^-1 (r=0.998 4-0.999 9). The average recoveries were 98.8%-100.3%. The limits of quantitation and detection were 0.5, 0.5, 0.05, 0.01 μg·L^-1 and 0.2, 0.2, 0.02, 0.005 μg·L^-1, respectively. CONCLUSION The method is rapid, sensitive and accurate, and can be an appropriate technique for quality control of compound glycyrrhiza oral solution.