Determination of the pKa values of β-blockers by automated potentiometric titrations

The acid base equilibrium constants of the beta-blockers atenolol, oxprenolol, timolol and labetalol were determined by automated potentiometric titrations. The pK(a) values were obtained in water-rich or water-methanol medium (20% MeOH) to obviate the solubility problems associated with the compounds. The initial estimates of pK(a) values were obtained from Gran's method and then, were refilled by the NYTIT and ZETA versions of the LETAGROP computer program. The resultant values were 9.4 (I = 0.1 M KCl, 20% methanol) for atenolol, 9.6 (I = 0.1 M KCl) For oxprenolol, 9.4 (I = 0.1 M KCl, 20% methanol) for timolol and 7.4 and 9.4 (I = 0.1 M KCl) for labetalol. The potentiometric method was found to be accurate and easily applicable. The operational criteria for applying the methodology are indicated. (C) 2000 Elsevier Science B.V. All rights reserved.