[Potentiometric determination of aqueous dissociation constants of 2-,3-,4-{3-(4-benzhydryl-piperazine-1-yl)-2-hydroxy-propoxy}-phenylcarbamic acid alkylesters, water insoluble potential blockers of beta-adrenergic receptors].

Apparent ionization constants (W(s)pK(a)) of potential drugs, a series of twelve protonated bases, 2-,3-,4-{3-(4-benzhydryl-piperazine-1-yl)-2-hydroxy-propoxy}-phenylcarbamic acid alkylesters dihydrochlorides, were determined by automated potentiometric titrations in mixtures water - methanol. Aqueous pK were assessed by means of Yasuda-Shedlovsky equation. Approach for pKa determination was evaluated using trimecaine hydrochloride as the model compound. The first values of ionization constants ranged approximately from 2.7 to 3.2, the second ones from 6.5 to 7.2. Only a slight decrease in ionization constants with the number of carbon atoms was observed in homological series. Experimentally determined dissociation constants were compared with the values predicted by the computer program SPARC.