An extensive study on the application of the "zero-crossing" technique for the analysis of a binary mixture of the photosensitive drug lacidipine and its corresponding by-product by derivative spectrophotometry is described. The technique has been compared to either conventional and recently developed UV spectrophotometric procedures, including chemometric methods. The prediction ability of the different analytical techniques has been checked by using the first-order derivative spectra of drug and photoproduct in binary mixtures. Relative advantages and drawbacks have been discussed. The zero-crossing technique suffers from several limitations, mostly ascribed to the selection of suitable signals along slopes of the spectral curve, giving rise to low accurate and precise results. The mean recovery from the zero-crossing analysis was calculated to lie in the 95.1-98.4% range for lacidipine, and 91.2-118.9% for the photoproduct. Chemometric methods showed a greater prediction ability with a 101.4-103.0% and 96.3-98.4% recovery for drug and degradation product, respectively.