The use of first derivative spectrophotometry for the simultaneous determination of certain drugs in multicomponent formulations is presented. The method is illustrated by the determination of antazoline hydrochloride, phenylephrine hydrochloride and ephedrine hydrochloride in eye drops and acepifylline, phenobarbitone and papaverine hydrochloride in suppositories. These selected applications illustrate the relative ease and simplicity offered by first derivative spectrophotometry for the assay of three-component mixtures with spectral interferences from matrix formulations.