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A sensitive ultra‐high performance liquid chromatography–tandem mass spectrometry method was developed and validated to clarify pharmacokinetic properties of 15 compounds (quercetin, isorhamnetin, chlorogenic acid, isoquercitrin, caffeic acid, scopoletin, 7‐hydroxycoumarin, shionone, ferulic acid, kaempferol‐7‐O‐β‐D‐glucopyranoside, methyl caffeate, luteolin, kaempferol, epifriedelinol, and protocatechuic acid) in raw and honey‐processed Aster tataricus. Separation was carried out on an ACQUITY UPLC®BEH C18 column (2.1 × 100 mm, 1.7 μm) using a gradient elution with mobile phase constituting 0.1% formic acid‐water and 0.05% formic acid‐methanol. Quantitative analysis was performed using multiple reaction monitoring detection in both positive and negative ionization modes. Calibration curves showed good linearity (r2 > 0.991) over the corresponding concentration range. The intra‐day and inter‐day precisions were within 10.1%, and accuracy ranged from ‐11.4% to 12.4%. The extraction recoveries and matrix effects were 78.1%–100.0% and 81.1%–113.7%, respectively. The analytes were stable under four storage conditions with relative standard deviations less than 12.6%. The validated method was successfully applied to compare the pharmacokinetic behaviors of raw and honey‐processed Aster tataricus for the first time. The results indicated that the AUCs of shionone, ferulic acid, and protocatechuic acid in honey‐processed Aster tataricus group were significantly lower than that of raw Aster tataricus group.

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