Polygonatum sibiricum F. Delaroche (P. sibiricum) is widely consumed as an ingredient in functional foods, drinking water, and tea. Its major constituent, azetidine-2-carboxylic acid (ACA), is a potent toxin that can be incorporated into proteins in place of proline, leading to protein dysfunction. Thus, quality control in the analysis of ACA in P.sibiricum is important for establishing guidelines for safe levels in foods. However, prior analyses of ACA in P. sibiricum are limited, and the few methods reported require complicated sample preparation. Here, for the quantitative analysis of ACA, we compare the traditional RPLC mode with the HILIC in HPLC. Then, we develop an ultraperformance liquid chromatography (UPLC) method to increase instrument sensitivity, using a CORTECS HILIC column. The developed method offers good linear correlation (r 2 > 0.9999), excellent precision (RSD < 1.6%), and acceptable recoveries (99.26-101.33%). The LOD and LOQ were 0.13 and 0.39 g/mL, respectively. The UPLC method using the HILIC column was much simpler because pre-purification is not required for the quantification of ACA. The proposed quantitative analysis method was Downloaded by [Texas A & M International University] at 16:52 16 August 2015 2reproducible and convenient, and our results provide reference information for the quality control of P. sibiricum as a component in consumable products.