Multiwavelength spectrophotometric determination of acid dissociation constants of ionizable drugs.

A multiwavelength spectrophotometric approach has been developed to determine acid dissociation constants (pKa values) of sparingly soluble drug compounds. UV absorption spectra of the drug solution are acquired using a versatile device based on a fiber optics dip probe, a light source and a photodiode array (PDA) detector while the PH and the ionic 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 pKa values from the multiwavelength UV absorption data recorded at different pH values. We have called this multiwavelength approach the WApH technique because the pKa results are determined from changes in Wavelength and Absorbance as a function of pH (WApH). The WApH technique is exemplified by using several pure drugs, namely, niflumic acid, nitrazepam, pyridoxine, quinine and terbutaline. The pKa values obtained agree well with those derived from pH-metric titrations. It has been demonstrated that the WApH technique is able to deduce pKa values with high accuracy even if the absorption spectra of the reacting species are very similar.