Abstract: By applying an ambient ionization-direct analysis in real time (DART) ion source tandem Orbitrap MS, a rapid screening method was developed for the determination and confirmation of sulfonamides drugs in animal feed. Through optimization of ionization temperature and sample injection modules, the screening method was established. Feed samples were extracted using 10 mL mixture of water and acetonitrile(3∶7,V/V) injected by transmission module, ionized under 450 ℃ and then analyzed using DART-Orbitrap MS in full scan mode. The results show that the limit of detection is 1.0—4.0 μg/g. This DART-Orbitrap MS method can be used for rapid and direct analysis of sulfonamides drugs illegally added in animal feed.