AbstractThis work aimed to evaluate the usefulness of ultra‐high‐performance liquid chromatography coupled with mass spectrometry for the simultaneous determination of five alkaloids and three main components of acetaminophen‐caffeine‐aspirin tablets in hot pot broth. The sample was extracted by hydrochloric acid (0.1 mol) and sodium hydroxide was used to adjust the potential of hydrogen. Then acetonitrile was used to extract the target compounds and cleaned up by one enhanced matrix removal product. Standard curves were made by adding mixing standard solutions of different concentrations. Eight isotope internal standards were used to improve the accuracy of the quantification. The linear ranges were 0.4–40.0 μg/kg for morphine, codeine, acetaminophen, caffeine, and salicylic acid, as well as 0.08–8.0 μg/kg for thebaine, papaverine, and noscapine, respectively. The eight compounds had good linearities and the detection limits of were in the range of 0.003–0.3 μg/kg. The recovery values were higher than 82% and the precision was lower than 14.7% in the experiment. A lot of actual testing of hot pot broth samples showed that the method is simple, effective, and sensitive, which is suitable for the determination and confirmation of the eight targeted compounds added to the hot pot broth.