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

The acid-base equilibria of several diprotic amphoteric drugs, namely, niflumic acid, norfloxacin: piroxicam, pyridoxine and 2-methyl-4-oxo-3H-quinazoline-3-acetic acid have been characterized in terms of microconstants and tautomeric ratios. A multiwavelength spectrophotometric (WApH) titration method for determination of acid dissociation constants (pK(a) values) of ionizable compounds developed previously was applied for this purpose. Microspeciation was investigated by three approaches: (1) selective monitoring of ionizable group by spectrophotometry, (2) deductive method and (3) k(z), method for determination of tautomeric ratio from co-solvent mixtures. The formulation for (3) has been derived and found to invoke fewer assumptions than 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 that the WApH technique, for such types of ampholytes, is able to deduce the microconstants and tautomeric ratios which are in good agreement with literature data. (C) 2000 Elsevier Science B.V. All rights reserved.