Abstract: Objective To investigate the detoxification of Aristolochia contorta Bge. in Zhisou Huatan pills via seed-removal and al kali-treatment based on quantitative determination of five aristolochic acid analogues in order to provide a reference for quality control. Methods The separation was performed on an ACQUITY UPLC BEH C₁₈ column (2.1 mm×50 mm, 1.7 μm) with methanol-water (containing 0.1% formic acid and 5.0 mmol·L^-1 ammonium acetate) as the mobile phases at a flow rate of 0.3 mL·min^-1. The multiple reaction monitoring mode (MRM) was used in positive ion acquisition. The established method was employed to quantitatively detect the contents of five aristolochic acid analogues in five batches of Aristolochia contorta Bge., ten batches of seed-removal Aristolochia contorta Bge., seed-removed and alkaline-processed Aristolochia contorta Bge., and in Zhisou Huatan pills. Results The contents of AAⅠ, AAⅡ, AAⅢa, AAⅣa, and ALⅠin Aristolochia contorta Bge. ranged from 573.12 to 880.72 μg·g^-1, 37.12 to 97.02 μg·g^-1, 236.68 to 461.83 μg·g^-1, 376.60 to 414.37 μg·g^-1 and 262.58 to 393.83 μg·g^-1, respectively. The content of AAⅡ was below the detection limit in seed-removed and alkaline-processed Aristolochia contorta Bge. but AAⅠ, AAⅢa, and AAⅣa could still be detected, and their concentrations were below the limit of quantification. The content of ALⅠ ranged from 25.15 to 35.29 μg·g^-1. AAⅠ, AAⅡ, AAⅢa, or AAⅣa were detected in Zhisou Huatan pills, and the content of ALⅠ ranged from 0.87 to 0.97 μg·g^-1. Conclusion Seed-removal and alkali-treatment can significantly reduce the contents of AAⅠ, AAⅡ, AAⅢa, AAⅣa, and ALⅠ in Aristolochia contorta Bge. AAⅠ is not detected in Zhisou Huatan pills. The established UPLC-MS/MS method has a high specificity, high sensitivity, and good repeatability, which can provide a reference for quality control of Zhisou Huatan pills.

Key words: Seed-Removal and Alkali-Treatment, Aristolochia contorta Bge., Zhisou Huatan Pills, Aristolochic Acids, UPLC-MS/MS, Quality Control