A prototype multiply hyphenated system has been applied to the analysis of a mixture of nonsteroidal antiinflammatory drugs separated by reversed-phase HPLC. Characterization of the model NSAIDs was achieved via a combination of diode array UV, 1H NMR, FT-IR spectroscopy, and time-of-flight mass spectrometry. This combination of spectrometers allowed the collection of UV, 1H NMR, IR, and mass spectra together with atomic composition data enabling almost complete structural characterization to be performed.