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5-O-Caffeoylquinic acid (5-CQA), also known as chlorogenic acid, exhibits various biological activities. Hence the interest in its property change during processing and extraction has increased. The present work studied the influence of ultrasound on the stability of 5-CQA at different pH (pH 4.69, 7.09, 7.69 and 9.22) in water and 50% methanol-water system. Different parameters including solvent, ultrasonic power, time, temperature, duty cycle, and liquid height were investigated during the treatment. Results indicate that ultrasound accelerated the degradation of 5-CQA. Based on Weibull model, the degradation kinetics were described. The rate constant (k) of the degradation increased with the increasing pH, demonstrating the alkali sensitivity of 5-CQA. The isomerization of 5-CQA to 3- and 4-O-caffeoylquinic acid was found at neutral and alkaline conditions, which was further boosted by ultrasound. The stability of 5-CQA was improved by adding epigallocatechin gallate (EGCG) and vitamin C (VC) respectively.