Determination of the pK(a) values of beta-blockers by automated potentiometric titrations

The acid base equilibrium constants of the beta-blockers atenolol, oxprenol ol, timolol and labetalol were determined by automated potentiometric titra tions. The pK(a) values were obtained in water-rich or water-methanol mediu m (20% MeOH) to obviate the solubility problems associated with the compoun ds. 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 comp uter program. The resultant values were 9.4 (I = 0.1 M KCl, 20% methanol) f or atenolol, 9.6 (I = 0.1 M KCl) For oxprenolol, 9.4 (I = 0.1 M KCl, 20% me thanol) for timolol and 7.4 and 9.4 (I = 0.1 M KCl) for labetalol. The pote ntiometric method was found to be accurate and easily applicable. The opera tional criteria for applying the methodology are indicated. (C) 2000 Elsevi er Science B.V. All rights reserved.