Donepezil HCl is a hydrochloride salt of a piperidine derivative acetylcholinesterase inhibitor and, ituses in treatment demantia of Alzheimer’s disease. In this study, a sensitive and rapid HPLC-UV method wasdeveloped and validated for determination of Donepezil HCl in API and tablet dosage forms. Chromatographicseparation was performed using a Ace 5 C18 (5 μm, 250 x 4.6 mm) by using isocratic phosphate buffer at pH:2.0and acetonitrile (55:45, v/v) mobile phase was used at the rate of 1.2 mL/min. The column temperature was set at30 C and the UV detection was recorded at 268 nm. The method was validated with respect to specificity,precision, accuracy, linearity, repeatability and reproducibility parameters in a concentration range of 25-125µg/mL. The limit of detection (LOD) and limit of quantification (LOQ) were determined as 1.40 and4.20 µg/mL,respectively. The uncertainty budget of the measurement for Donepezil HCl was estiamted as 5.80 % at 95%confidence level (k = 2).