Multiwavelength spectrophotometric determination of acid dissociation constants Part III. Resolution of multi-protic ionization systems

A multiwavelength spectrophotometric (WApH) titration method was applied to study several multi-protic histamine H-2-receptor antagonists which involv ed four acid dissociation constants (pK(a) values) over the pH range of 2-1 0. Specifically, UV absorption spectra of the drug solution were acquired i n the course of a pi-I-metric titration using an optical device based on a fibre optics dip probe, a light source and a diode array detector. Target f actor analysis was utilized to deduce the pK(a) values from the spectral da ta recorded at different pH. It was noted that some of the pK(a) values wer e within mid pH range which were difficult to obtain because of insufficien t absorption spectra acquired in the un-buffered region of the titration cu rve. With the aid of the WApH technique coupled with an optically transpare nt buffer, all pK(a) values have been successfully determined and were in e xcellent agreement with those measured using a conventional pH-metric metho d. (C) 1999 Elsevier Science B.V. Al rights reserved.