A new ultra-performance liquid chromatographic (UPLC) method has been developed and validated for quantification of substances related to varenicline tartrate, process-related and degradation products, in pharmaceutical formulations. Chromatographic separation of six impurities was performed on a reversed phase column. The method was validated for linearity, limits of detection and quantification, accuracy, precision, and selectivity. The calibration plots obtained for the six impurities were linear over the range 0.005–0.30%. The relative standard deviations ( s r) of intra and inter-day experiments were less than 1.0%. The detection limits ranged between 0.002 and 0.004%, depending on the impurity. The proposed UPLC method was successfully applied to quantification of varenicline impurities in its pharmaceutical formulation.