The ratio spectra derivative spectrophotometry was applied for the simultaneous determination of chlordiazepoxide (CH) with clidinium bromide (CL), pipenzolate bromide (PI) or amitriptyline hydrochloride (A) in binary mixtures. The analytical signals were measured at 243.1 and 214.8 nm in the CH-CL mixture, 271.4 and 256.7 nm in the CH - PI mixture, and 264.9 and 218.0 nm in the CH-A mixture for CH and its co-existing compounds, respectively, in the first derivative mode in methanol. Calibration graphs were established for 2.0 - 38.0 μml−1CH and 4.0 - 20.0 μgml−CL in CH - CL mixture, for 2.0 - 38.0 μgml−1CH and 4.0 - 32.0 μgml−1PI in CH - PI mixture, and for 2.0 - 28.0 μgml−1CH and 4.0-36.0 μgml−1A in CH - A mixture. The method was successfully applied to the pharmaceutical formulations containing the above-mentioned drug combinations without any interference by the excipients. Vierordt's method was also developed for a comparison method.