The polarographic and spectral behaviour of some 1,4-benzodiazepine metabolites: application to differentiation of mixtures

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Abstract
Changes of ultraviolet absorption spectra with pH in solution were used to determine pKa values for four 1,4-benzodiazepine metabolites. 7-Acetamido-nitrazepam, desmethyl-diazepam and the chlordiazepoxide lactam all gave two pKa values, corresponding to protonation in acid and deprotonation of the neutral molecule in alkaline media. 7-Amino-nitrazepam gave three pKa values, the third one being due to an additional protonation in acid media. The spectra are explained by considering them to be superimposed spectra of the two benzene rings, one mono-substituted (band I) and one trisubstituted (band II), within the molecule. Sites of protonation and deprotonation are predicted and the differences in the observed pKa values explained. Differences in the pKa values or the polarographic behaviour between the parent compounds and some of their metabolites are then used to effect novel separations after solvent extractions from aqueous buffered solutions.