Two highly sensitive methods for the determination of genotoxic alkyl methane sulfonates (AMSs) and alkyl paratoluene sulfonates (APTSs) in lamivudine using hyphenated techniques have been presented.AMSs were determined by GC-MS method using GSBPINOWAX (30 m × 0.25 mm × 0.25 μm) column.Temperature program was set by maintaining at 100 ℃ initially for 3 min,then rised to 220 ℃ at the rate of 15 ℃/min and maintained at 220 ℃ for 16 min.N,N-dimethyl formamide was used as diluent.APTSs were determined by LC-MS using Zorbax,Rx C8,250 mm × 4.6 mm,5 μm column as stationary phase.0.01 M ammonium acetate is used as buffer.The mixture of buffer and methanol in 75∶25 (v/v) ratio was used as mobile phase A and mixture of buffer and methanol in 5∶95 (v/v) ratio was used as mobile phase B.The gradient program (T/%B) was set as 0/28,16/50,17/100,23/100,27/28 and 40/28.Both the methods were validated as per International Conference on Harmonization guidelines.Limit of quantitation was found 1.5 μg/mL for AMSs and was in the range of 1.0-1.5 μg/mL for APTSs.