PH-METRIC LOG-P .4. COMPARISON OF PARTITION-COEFFICIENTS DETERMINED BY HPLC AND POTENTIOMETRIC METHODS TO LITERATURE VALUES

The pK(a) and log P of 20 compounds, including six substituted phenols , two substituted quinolines, N-methylaniline, five barbiturate deriva tives, two phenothiazines, and several other molecules of pharmaceutic al interest, were determined by the potentiometric technique at 25 deg rees C and ionic strength 0.1 M (KNO3). The log P values were determin ed also by partition HPLC. Three of the substances were of very low aq ueous solubility, and for these the aqueous pK(a)s were determined by extrapolation from methanol-water solutions using the Yasuda-Shedlovsk y technique. Values of log P obtained both by potentiometry and by par tition HPLC, which ranged from 0.3 to 5.4, were in very good acordance with literature values. The general applicability of the potentiometr ic technique to ionizable compounds of diversely varied structures was demonstrated by the study.