Vibrational and NMR Spectroscopic Study of Aged Flurazepam Mono- and Dihydrochloride Salts for Content Identity

Archival samples of flurazepam monohydrochloride and “hydrochloride” (i.e., the dihydrochloride) were examined by Fourier transform infrared and Raman spectroscopy to determine evidence of degradation during storage for 13–15 years. No degradation of the three different batches of monohydrochloride salts was detected, but various degrees of degradation of the eight specimens of flurazepam hydrochloride diprotonated salts were indicated by enhanced intensities (IR 1635, 1509, 1226; Raman 1636, 1408, 1149 cm−1) and new features (IR 1742, 943, 755; Raman 1554, 837, 742 cm−1). All of these features, except the 1742 cm−1IR band, were attributed to the presence of the hydrolysis product 5-chloro-2-[[2-(diethylamino)ethyl]amino]-2′-fluorobenzophenone hydrochloride whereas the 1742 cm−1band was attributed to glycine hydrochloride, the other hydrolytic moiety. The flurazepam hydrochloride samples were also examined in deuterated dimethyl sulfoxide solution by proton nuclear magnetic resonance (1H-NMR) spectroscopy to verify the presence of the degradation products and to estimate the levels of degradation (∼3–36%) of the drug. IR and Raman spectra of the “benzophenone” hydrochloride in the “fingerprint” region are compared with two samples of flurazepam dihydrochloride (slightly and highly degraded) and their features discussed. Vibrational assignments are made and discussed for the observed IR and Raman wavenumbers for the “benzophenone” hydrochloride.