In this study, a rapid, environmental, economical, and practical method, polyethylene glycol (PEG) assisted mechanical amorphous dispersion using water for the extraction of hydrophobic anthraquinones in crops was first proposed. In order to fully understand the factors affecting the extraction yield, a systematic study was carried out by single factor tests and response surface methodology (RSM). The corresponding influence parameters including the type of dispersant, the amount of dispersant, grinding time, extraction time, and solid-liquid ratio were optimized. Subsequently, RSM was used for multifactor experiments and the optimum conditions were 242.67 mg of PEG 100000, 4.91 min of grinding time, 4.60 min of extraction time, and 10 mL of water, respectively. To verify the feasibility of this method, the solution extracted was then analyzed by high performance liquid chromatography/quadrupole-time of flight mass spectrometry. The results showed that this method had good linearity (R2 higher than 0.99), stable intra-day precision, and inter-day precision with relative standard deviations ranging from 0.04 to 2.07% and 0.22–3.00%, satisfactory reproducibility of 0.02–6.23% for all analytes. Finally, this method was successfully used for the extraction and analysis of anthraquinones from aloe.
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