Abstract: A method for the determination of 21 antihistamines in cosmetics by UHPLC-MS/MS was established. Samples were extracted with methanol, then 21 components were separated on an Waters ACQUITY UPLC BEH-C₁₈ column with mixed solution composed of methanol and 0.1% (volume fraction) formic acid solution (containing 0.1 mol·L^-1 ammonium formate) as mobile phase for gradient elution. Detection was carried out by ESI⁺ in MRM mode in MS/MS analysis. Linearity relationships between mass concentrations of the 21 antihistamines and their peak areas were kept in the same range of 5-250 μg·L^-1, with detection limits (3S/N) in the range of 0.1-0.5 μg·L^-1. The recoveries on three substrates were found in the range of 80.2%-110%, with RSDs (n=6) of determined values ranged from 1.5% to 7.9%. The proposed method was applied for the analysis of 50 batches of mask samples, and none of 21 antihistamines were found.