Desloratadine (DL) is a classic antihistamine for treating allergic rhinitis and chronic urticaria. When the structure-related N—H bond is studied using spectroscopy, different pretreatment and testing methods significantly affectthe characteristic absorption peaks with the corresponding height ratio. With Fourier transform infrared transmission method (TR-FTIR), the spectra of DL show obvious differentiation at 3 325 and 3 304 cm-1 two characteristic absorption peaks with peak height ratio of 1∶1, no peak, at 3 327 and 3 304 cm-1 two peaks with peak height ratio of 1∶2.3 respectively corresponding to three different pretreatments of conventional potassium chloride tablet, nujol mull, potassium chloride tablet with nujol mull. Furthermore, the characteristic peaks assigned N-H stretching vibration can hardly be detected using attenuated total reflection FTIR (ATR- FTIR) accessory with neither the crystal type of ATR nor the detector of the instrument changed, indicating the sensitivity of detector also plays an important role. Subsequently, using the diffuse reflection spectrum FTIR method (DRS-FTIR), it is easy to find two characteristic absorption peaks at 3 327 and 3 304 cm-1 with a peak height ratio of 1∶5 without any pretreatment. For the Fourier transform Raman (FT-Raman), two absorption peaks at 3 327 and 3 304 cm-1with a higher peak height ratio of 1∶6 also can be achieved at a high signal-to-noise ratio without pretreatment. For the Laser Raman with the excitation wavelengths of 532, 633 and 785 nm, no useful signal can be observed above 1 700 cm-1 because of the strong fluorescence. To analyze the effect of pretreatment on the IR N—H band of DL further, differential scanning calorimetry (DSC) is applied to detect the melting point change in the current study. The melting points of 156.4, 156.6 and 156.6 ℃ of the raw DL, the grinding DL and the mixture of DL and KCl indicate that the physical processes of grinding and mixture cannot destroy the crystalline from of DL. The melting points of 153.0, 141.5 and 145.0 ℃ for the ground samples of mixed DL and KCl, mixed with paraffin, and mixed with paraffin and KCl are lower than the raw DL with a broader distance of DSC peaks and indicate the structure change of DL during pretreatment. Therefore, DRS-FTIR and FT-Raman are the suggested methods forspectrum detection to avoid the uncertainty introduced by pretreatment of DL.