Abstract: OBJECTIVE To establish an LC-QQQ-MS/MS method for the determination of trace genotoxic impurities of benzenesulfonate esters including methyl benzenesulfonate, ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate in amlodipine besilate. METHODS Agilent Zorbax SB-C₁₈(3.0 mm×100 mm, 1.8 μm) analytical column was used for the separation with a mobile phase of water(5 mmol·L^-1 ammonium formate and 0.1% formic acid) and methanol (5 mmol·L^-1 ammonium formate and 0.1% formic acid) at a flow rate of 0.4 mL·min^-1 in gradient elution mode. The method was developed at ESI(+) with MRM mode. RESULTS The LOQ of methyl benzenesulfonate, ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate were 20, 1, 1, 1 ng·mL^-1, respectively. The method had good precision, the RSD of retention time and peak area were both <5% for the four target compounds(n=10). The linearity range of methyl benzenesulfonate was 20-1 000 ng·mL^-1, the linearity ranges of ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate were all 1-1 000 ng·mL^-1, with the excellent correlation coefficient(r) ≥ 0.998. The method had good accuracy, average recoveries(n=10) were 99.77%, 100.19%, 94.21% and 92.43%, respectively. The contents of methyl benzenesulfonate in amlodipine besylate samples from five different manufacturers were all -1), the contents of ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate were all -1). CONCLUSION The established method can be applied to the determination of trace genotoxic impurities of benzenesulfonate esters (methyl benzenesulfonate, ethyl benzenesulfonate, propyl benzenesulfonate, isopropyl benzenesulfonate) in amlodipine besylate.