The present article describes strategic method development and validation for the determination of fifteen known potential impurities present in levodopa, carbidopa, and entacapone in fixed dose combination drug product using reverse phase-ultra performance liquid chromatography (RP-UPLC). Effective and rapid separation between impurities at satisfactory level is achieved in Acquity UPLC BEH C₁₈, 100 mm length × 2.1 mm id with 1.7 µm particle size. Flow gradient elution mode was kept using 0.1% Perchloric acid in water as Mobile phase A and acetonitrile as Mobile phase B. Initial flow rate was maintained at 0.5 mL.min⁻¹, followed by a gradual increase to 0.7 mL.min⁻¹. Monitoring wavelength was fixed at 225 nm. Developed method was successfully validated as per method validation parameters recommended by the International Conference on Harmonisation (ICH) for specificity, linearity, precision, accuracy, determination of LOD and LOQ, solution stability, and robustness. The developed and validated method uses less consumption of solvents and a shorter run time of 20 min results in a rapid, precise, sensitive, cost, and time effective method for the quantitative determination of levodopa, carbidopa, and entacapone impurities in levodopa, carbidopa, and entacapone tablets dosage form helping the quality control laboratory analysts to release the batches at faster rate at commercial stage and to assure therapeutic efficacy using single method for all three drug components of levodopa, carbidopa, and entacapone.