Acid-Base and Spectroscopic Properties of 1,4-Benzodiazepines in Sodium Dodecyl Sulfate Micellar Solutions

Acid-base equilibria and spectroscopic properties of diazepam and chlorodiazepoxide were investigated in sodium dodecyl sulfate (SDS) micellar solutions as functions of pH. The results were compared with the behaviors in homogeneous aqueous media. The presence of SDS increased the $pK_a$ of chlorodiazepoxide to 6.3 from 4.7, while it has little effect on the $pK_a$ of diazepam. The acidic protonated form of diazepam was moderately fluorescent when the solution was excited at 350 nm, and emissnion intensity of the species was enhanced about 5 fold by the presence of SDS. On the other hand, the acidic solution of chlorodiazepoxide was non-fluorescent, but the neutral solution of the compound was fluorescent upon excitation at 350 nm. The emission peak of the neutral chlorodiazepoxide shifted to shorter wavelength region without significant change in the emission intensity upon the addition of SDS. Procedures for assay of the individual drugs from their mixture by the use of SDS micelle were discussed.