The present study for online extraction of fifteen sulfonamide residues from honey by short C-18 column, usually used as guard column, was proved to be an excellent method. Moreover, the use of minimal volume of organic solvent makes the method environment-friendly and therefore, decreases the disposal costs.Furthermore, we also applied our developed method to 0.5 g ofhoney sample spiked at 100 ng g−1 for n = 3 (data was not included in this article). This further reduces the utilization of reagent in sample pretreatment and makes this method economical. Also, the online extraction of sulfonamide residues from honey matrix using enhanced retention of sulfonamides drugs by derivatization with fluorescamine on reverse phase C-18 column makes the present method unique. In addition, the large volume injection was made possible (Fig. 5) by the present study which can further decrease the LOD and LOQ up to pico gram per gram of sulfonamide residuesin honey sample, as per demand of present era or legislative authority, which makes the present method highly sensitive. Moreover,the use of guard column as an online extraction component makes this method further economical and is crucial to obtain reliable and reproducible results as well as high absolute recoveries. The present method is well suited to quantify the studied sulfonamide residues in honey at concentration levels below the maximum residues limits endorsed by the European Countries, United State and Canada.