A unique and generic strategy has been developed to the analysis of complex materials containing the polar and non-polar components.The approach operated by employing serial and parallel coupling of threecolumns in the high performance liquid chromatography system.The present two-dimensional HPLC strategy produces high resolution with low retention factor which is the ideal state in chromatography.Here,the polar and non-polar sample components were divided into two parts on the basis of relative polarity by employing a short reverse phase.Each part of the sample was subjected to further separation by two analytical columns.After developing the two-dimensional HPLC strategy,we have applied it on fourbeta-blocker tablet samples containing active and inactive pharmaceutical ingredients.In this system,the active and inactive ingredients in the tablet sample can be analyzed independently by using two second dimension columns with two different types of detectors.