In the present work, four different spectrophotometric methods for simultaneous estimation of losartan potassium, amlodipine besilate and hydrochlorothiazide in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods, classical least squares (CLS), multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix, with measurements in the range of 230.5-350.4 nm (δλ = 0.1 nm) in their zero order spectra. The linearity range was found to be 8-40, 1-5 and 3-15 μg mL-1 for losartan potassium, amlodipine besilate and hydrochlorothiazide, respectively. The validity of the proposed methods was successfully assessed for analyses of drugs in the various prepared physical mixtures and in tablet formulations.