Potentiometric determination of acid dissociation constants (pKa) for human and veterinary antibiotics

This work determined the acid dissociation constants (pK(a)) of 26 common human and veterinary antibiotics by potentiometric titration. Selected antibiotics consisted of sulfonamides, macrolides, tetracyclines, fluoroquinolones, and other miscellaneous antibiotics. After validation of analysis methods using phosphoric acid as a model compound, a second-derivative (Delta(2)pH/DeltaV(2)) method was primarily applied to determining pK(a)'s from titration curves for most antibiotics due to its convenience and accuracy. For tetracyclines, however, a least-square non-linear regression method was developed to determine their pK(a)'s because the second-derivative method cannot well distinguish the pK(a,2) and pK(a,3) of tetracyclines. Results indicate that the pK(a) values are approximately 2 and 5-7.5 for sulfonamides; 7.5-9 for macrolides; 3-4, 7-8 and 9-10 for tetracyclines; 3-4, 6, 7.5-9 and 10-11 for fluoroquinolones; while compound-specific for other miscellaneous antibiotics. The moieties corresponding to specific pK(a)'s were identified based on chemical structures of antibiotics. In addition, the pK(a)'s available in literature determined by various techniques are compiled in comparison with the values of this work. These results are expected to essentially facilitate the research on occurrence, fate and effects, analysis methods development, and control of antibiotics in various treatment operations. (C)# 2004 Elsevier Ltd. All rights reserved.