Two multivariate calibration-prediction techniques, principal component analysis (PCR) and partial least squares (PLS) were applied to the spectrometric multicomponent analysis of the drug containing lansoprazole (LAN) and domperidone (DOM) without any separation step. The selection of variables was studied. A series of synthetic solution containing different concentrations of LAN and DOM were used to check the prediction ability of the PCR and PLS. The results obtained in this investigation strongly encourage us to apply these techniques for a routine analysis and quality control of the two drugs.