VIBRATIONAL AND NMR SPECTROSCOPIC STUDY OF AGED FLURAZEPAM MONOHYDROCHLORIDE AND DIHYDROCHLORIDE SALTS FOR CONTENT IDENTITY

Archival samples of flurazepam monohydrochloride and ''hydrochloride'' (i.e., the dihydrochloride) were examined by Fourier transform infrar ed 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 degra dation of the eight specimens of flurazepam hydrochloride diprotonated salts were indicated by enhanced intensities (IR 1635, 1509, 1226; Ra man 1636, 1408, 1149 cm(-1)) and new features (IR 1742, 943, 755; Rama n 1554, 837, 742 cm(-1)). All of these features, except the 1742 cm(-1 ) IR band, were attributed to the presence of the hydrolysis product [ 2-(diethylamino)ethyl]amino]-2'-fluorobenzphenone hydrochloride wherea s the 1742 cm(-1) band was attributed to glycine hydrochloride, the ot her hydrolytic moiety. The flurazepam hydrochloride samples were also examined in deuterated dimethyl sulfoxide solution by proton nuclear m agnetic resonance (H-1-NMR) spectroscopy to verify the presence of the degradation products and to estimate the levels of degradation (simil ar to 3-36%) of the drug. IR and Raman spectra of the ''benzophenone'' hydrochloride in the ''fingerprint'' region are compared with two sam ples of flurazepam dihydrochloride (slightly and highly degraded) and their features discussed. Vibrational assignments are made and discuss ed for the observed IR and Raman wavenumbers for the ''benzophenone'' hydrochloride.