DETERMINATION OF DISSOCIATION-CONSTANTS OF SPARINGLY SOLUBLE PHENOTHIAZINE-DERIVATIVES BY 2ND-DERIVATIVE SPECTROPHOTOMETRY

The dissociation constants (pK(a)) for sparingly soluble phenothiazines (promazine, chlorpromazine, trifluoropromazine) in water were measured by second-derivative spectrophotometry. The intense background signals in the absorption spectra due to the turbidity caused by the precipitation of insoluble free base of the phenothiazine derivatives were eliminated in the second-derivative spectra, and the solubilities of the phenothiazine derivatives could be easily determined from the peak-to-trough lengths (D values) of the second-derivative signals. The pK(a)) values were calculated from the pH dependence of the D values. The pK(a)) values obtained agreed well with reported values and the standard deviations for 6-10 determinations were less-than-or-equal-to 0.02. The solubilities of the free bases of the phenothiazines were also determined.