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 involved four acid dissociation constants (pK(a) values) over the pH range of 2-10. Specifically, UV absorption spectra of the drug solution were acquired in 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 factor analysis was utilized to deduce the pK(a) values from the spectral data recorded at different pH. It was noted that some of the pK(a) values were within mid pH range which were difficult to obtain because of insufficient absorption spectra acquired in the un-buffered region of the titration curve. With the aid of the WApH technique coupled with an optically transparent buffer, all pK(a) values have been successfully determined and were in excellent agreement with those measured using a conventional pH-metric method. (C) 1999 Elsevier Science B.V. Al rights reserved.