A Fourier transform-Raman and IR vibrational study of flurazepam base and the mono- and dihydrochloride salts.

Fourier transform (FT) Raman and IR spectra of flurazepam base and the mono- and dihydrochloride salts have been recorded. The parent compounds is 7-chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-[2H]- 1,4-benzodiazepin-2-one and is closely related to diazepam. The spectra show characteristic features associated with both the diazepine ring and substituents. Very strong lines near 1615 cm-1 in the Raman spectra of the base and the monohydrochloride are assigned to the C = N stretch of the diazepine ring. The C = N group becomes a C = N+ group in the dihydrochloride and the frequency shifts to 1635 cm-1. A very strong absorption near 1680 cm-1 in the IR spectra of the three compounds is attributed to the C = O stretching mode. The hydrochlorides are characterized by very strong broad bands in the IR spectra between 2600 and 2200 cm-1. Various IR and Raman vibrational features serve to characterize and differentiate the salts from each other and the free base. Raman and IR spectra have also been recorded for the related compound desalkylflurazepam [7-chloro-5-(2-fluorophenyl)-1,3-dihydro-[2H]-1,4-benzodiazepin-2- one], in which a hydrogen atom replaces the (diethylamino)ethyl group at position 1 of the diazepine ring. Comparison of the spectra of this compound with those of flurazepam has enabled some vibrations of the (diethylamino)ethyl group to be identified.

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-1 IR band, were attributed to the presence of the hydrolysis product 5-chloro-2-[[2-(diethylamino)ethyl]amino]-2'-fluorobenzophenone hydrochloride whereas the 1742 cm-1 band 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 (approximately 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.

A Fourier transform-Raman and infrared vibrational study of delorazepam, fludiazepam, flurazepam, and tetrazepam.

Fourier transform-Raman and IR spectra of four compounds that are closely related to diazepam (Valium) have been recorded. The compounds, delorazepam, fludiazepam, flurazepam, and tetrazepam, are all 7-chloro-1,3-dihydro-[2H]-1,4-benzodiazepine -2-ones and differ from diazepam by the substituents at positions 1 and 5 of the diazepine ring. The spectra show characteristic features associated with both the diazepine ring and substituents. A strong line near 1610 cm-1 in the Raman spectra is assigned to the C = N stretch of the diazepine ring, and very strong IR absorption near 1690 cm-1 is attributed to the C = O stretching mode. Various IR and Raman vibrational features serve to characterize and differentiate these molecules. Evidence for intermolecular hydrogen bonding in one of the compounds (delorazepam) is presented.

Utility of Fourier transform-Raman and Fourier transform-infrared diffuse reflectance spectroscopy for differentiation of polymorphic spironolactone samples.

Thirteen bulk pharmaceutical preparations of spironolactone were examined by Fourier transform (FT)-Raman spectroscopy and by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) for residual solvents (including the hydrolysis product, thioacetic acid), the presence of enolic tautomeric forms, and evidence for different polymorphic forms. One sample (L) only was found to contain solvent residue (benzene). No evidence for the possible existence of enolic tautomers in the solid state was found. From these specimens, four different representative polymorphic samples (A, B, C, and D) were selected on the basis of their DRIFTS patterns in the 3600-3200-cm-1 region. Samples K and L were considered to represent mixtures of two or more of the above representative types. Similar differentiation of the samples was made on the basis of their Raman spectra over the frequency range 1800-400 cm-1. The various fundamental stretching frequencies for the C = O and C = C bonds have been assigned, and these assignments, in turn, were used to account for all the bands in the 3600-3200-cm-1 region as overtone and combination frequencies of the fundamentals. The Raman lines at 637 and 655 cm-1 were assigned to the two C-S stretching modes of the thioacetyl moiety.

The examination of illicit cocaine.

A laboratory system of examination of illicit cocaine exhibits is described. Separation and identification of many of the components in exhibits are achieved by the use of capillary column gas chromatography and a Finnigan ion trap detector. Further examination and quantitation of the components of exhibits is achieved using two high performance liquid chromatographic (HPLC) systems. Both of these systems use identical reverse phase C8 columns. System 1 employs a solvent composed of 40% acetonitrile, 10% tetrahydrofuran and 50% 0.1% v/v aqueous triethylamine. The eluant is monitored at 280 nm. This system is preferred for routine quantitative analysis of cocaine and related alkaloids in exhibits. System 2 employs a solvent composed of 30% acetonitrile and 70% 0.05M phosphate buffer (pH = 5.0). The eluant from this system is monitored at both 220 and 280 nm. This system offers advantages in sensitivity. The relative retention times of a number of relevant substances as determined with gas chromatography and the two HPLC systems are given. The utility of the methodology for the identification and comparison of exhibits is demonstrated.