Determination of the dissociation constants of the cephalosporins cefepime and cefpirome using UV spectrometry and pH potentiometry

UV spectrometry and pH potentiometry were used for the determination and direct characterization of the dissociation constants of cefepime (Cef) and cefpirome. The absorbance/pH profiles at two analytical wavelengths and different conditions were assessed and found to conform to those of diprotic acids. The titration curves indicated a triprotic acid profile with two overlapping dissociation constants. The comparison of the results of both techniques permitted the direct attribution of the three dissociation constants to the carboxylic group at position 4 of the Delta-3 cephem nucleus, the aminothiazole group and the amide group at position 7 of the Delta-3 cephem nucleus. Stability studies of Cef in alkaline solutions were also performed in order to evaluate the accuracy of the measurements carried out for the determination of the third pK(a),, value. The experimental pK(a),, values were compared to the corresponding predicted values derived by PALLAS/PKALC and Advanced Chemical Development (ACD) software packages. (C) 2003 Elsevier Science B.V. All rights reserved.