¹Department of Pharmaceutical Analysis, College of Pharmaceutical Sciences,Andhra University,Vishakapatnam 530003,India DOI : 10.29228/jrp.259 Using an LC-MS/MS (liquid chromatography-tandem mass spectrometry) method, four probable genotoxic impurities (PGIs) in the varenicline were quantified. With 0.7 mL/min of flow rate, the separation was performed using a Phenomenex kinetex F5 100 column (150 x 4.6 mm I.D., 2.6 μm) in gradient elution mode with formic acid of 0.1 percent in water as mobile phase A and formic acid of 0.1 percent in methanol as mobile phase B. MMR mode (Multiple reaction monitoring) is utilized to measure impurities with triple quadrupole mass detection using electrospray ionization. For all five PGIs, the approach was thoroughly verified as per ICH guidelines. In each case, this correlation coefficient was greater than 0.998. The recoveries for all chosen impurities were determined to be good, ranging between 83.7 to 107.3 percent. At a concentration level of 0.521-0.549 ppm, the proposed approach was sensitive enough to quantify all five PGIs. As a result, the proposed method for identifying and quantifying PGIs in varenicline is both practical and effective. Keywords : Varenicline; genotoxic impurities; liquid chromatography-tandem mass spectrometry; sensitive