MULTIWAVELENGTH SPECTROPHOTOMETRIC DETERMINATION OF ACID DISSOCIATION-CONSTANTS OF IONIZABLE DRUGS

A multiwavelength spectrophotometric approach has been developed to de termine acid dissociation constants (pK(a) values) of sparingly solubl e drug compounds. UV absorption spectra of the drug solution are acqui red using a versatile device based on a fiber optics dip probe, a ligh t source and a photodiode array (PDA) detector while the pH and the io nic strength of the chemical system is manipulated precisely by means of a commercially available titrator. Target factor analysis (TFA) has been applied to deduce the pK(a) values from the multiwavelength UV a bsorption data recorded at different pH values. We have called this mu ltiwavelength approach the WApH technique because the pK(a) results ar e determined from changes in Wavelength and Absorbance as a function o f pH (WApH). The WApH technique is exemplified by using several pure d rugs, namely, niflumic acid, nitrazepam, pyridoxine, quinine and terbu taline. The pK(a) values obtained agree well with those derived from p H-metric titrations. It has been demonstrated that the WApH technique is able to deduce pK(a) values with high accuracy even if the absorpti on spectra of the reacting species are very similar. (C) 1998 Elsevier Science B.V. All rights reserved.