In this study, a strong applicable method that could determine a total of 33 pesticides (54 compounds), 11 mycotoxins and functional components (ferulic acid) simultaneously in Angelica sinensis was developed. The compatibility of the sample pretreatment method for pesticides, mycotoxins, and functional components was improved by optimizing the acidity of extraction solvents, the sequence of ice bath and oscillation, the volumetric solution, and so on. The PRiME HLB SPE pretreatment method was chosen as the optimal one when comparing four pretreatment methods. Among the 65 contaminants, 38 of those determined by liquid chromatography and 41 of those by gas chromatography, which showed good linearity (R2 > 0.9801), 97 % of them had a limit of quantitation (LOQ) of lower than 0.02 mg kg-1. The recovery of all compounds were suited between 70 % to 120 % and the RSD were all lower than 20 % at the spiked levels of LOQ, 2 × LOQ, and 10 × LOQ. For ferulic acid, the LOQ was 50 ng/mL, and it showed good linearity (R2=0.9988) within the range of 0.5 to 10 μg/mL. The recovery and RSD were 98.1 %, and 3.2 % (n = 6), respectively. The simultaneous determination of cross-category compounds in a single sample preparation was obtained by the combination of SPE and GC/LC-Q-TOF/MS. Therefore, this study could not only shorten the time for data acquisition and data analysis, but also improve the experimental efficiency.