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

Abstract

A multiwavelength spectrophotometric (WApH) titration method was applied to study several multi-protic histamine H 2-receptor antagonists which involved four acid dissociation constants (p K a values) over the pH range of 2–10. Specifically, UV absorption spectra of the drug solution were acquired in the course of a pH-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 p K a values from the spectral data recorded at different pH. It was noted that some of the p K 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 p K a values have been successfully determined and were in excellent agreement with those measured using a conventional pH-metric method.