Abstract: Astragalus polysaccharides (APS), as an important active component of traditional Chinese medicine, have impurities such as monosaccharides and phenolic acids remaining during its production process, which seriously affect the safety and efficacy of the drug. In order to control its quality, this study aimed to establish an analytical method for the simultaneous detection of trace monosaccharides and phenolic acids impurities in APS. A multi-dimensional detection method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established. The gradient elution program (acetonitrile -5 mmol/L ammonium formate, pH 4.5) was optimized by hydrophilic interaction chromatography (HILIC), and combined with the multi-reaction monitoring mode (MRM) of triple quadrupole mass spectrometry,the precise separation and quantification of monosaccharides (glucose, galactose) and phenolic acid (protocatechuic acid, caffeic acid) impurities were achieved. Methodological validation indicated that the detection limit of the target substance was 0.03-0.08 ng/mL, the linear range was 0.2-50 ng/mL (R²≥0.999 3), the recovery rate was 93.7%-104.1%, and the precision RSD was ≤5.5%. The actual sample tests showed that the total impurity content (4.5-5.2 μg/g) of the three batches of APS met the pharmacopoeia standards. This method broke through the bottleneck of traditional analytical techniques and provided key technical support for the "component-impurity" dual-standard quality control system of polysaccharide components in traditional Chinese medicine.

Key words: ultra-performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）, Astragalus polysaccharides（APS）, impurity analysis, quality control