Multiwavelength spectrophotometric determination of acid dissociation constants - Part V: microconstants and tautomeric ratios of diprotic amphotericdrugs

The acid-base equilibria of several diprotic amphoteric drugs, namely, nifl umic acid, norfloxacin: piroxicam, pyridoxine and 2-methyl-4-oxo-3H-quinazo line-3-acetic acid have been characterized in terms of microconstants and t automeric ratios. A multiwavelength spectrophotometric (WApH) titration met hod for determination of acid dissociation constants (pK(a) values) of ioni zable compounds developed previously was applied for this purpose. Microspe ciation was investigated by three approaches: (1) selective monitoring of i onizable group by spectrophotometry, (2) deductive method and (3) k(z), met hod for determination of tautomeric ratio from co-solvent mixtures. The for mulation for (3) has been derived and found to invoke fewer assumptions tha n a reported procedure (K. Takacs-Novak, A. Avdeef, K.J Box, B. Podanyi, G. Szasz, J. Pharm. Biomed. Anal., 12 (1994) 1369-1377). It has been shown th at the WApH technique, for such types of ampholytes, is able to deduce the microconstants and tautomeric ratios which are in good agreement with liter ature data. (C) 2000 Elsevier Science B.V. All rights reserved.