DETERMINATION OF DISSOCIATION-CONSTANTS AND PARTITION-COEFFICIENTS OF PHENOTHIAZINE-DERIVATIVES

A method of determining the dissociation constants of lipophilic weak acids or bases of low aqueous solubility based oh the measurement of the pH dependency of partition coefficients is described. The measurements, although subject to the possibility of error due to the partitioning of impurities, are free from the errors of extrapolation involved in mixed solvent titrimetric or solubility methods for the determination described m the literature. Precise spectrophotometry is essential, in the method described, but this coupled with a large number of data points can lead to a precision of < ± 0.03 in pKa.The cyclohexane/water partition coefficients of 8 phenothiazines measured during the course of this work are discussed in terms of published affinity constants for plasma proteins and support the view of the hydrophobic nature of drug-binding to plasma. © 1979.