Determination of the Optimum pH for Isolation of a Compound with Multiple pKa's from Aqueous−Organic Solvent Mixtures

Potentiometric titration of (4R,5S,6S,8R,2‘S,4‘S)-3-[[2-[[(3-carboxyphenyl)amino]carbonyl]pyrrolidin-4-yl]thio]-4-methyl-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-en-2-carboxylic acid, a broad-spectrum antibiotic, in several solvent systems was used to generate values for the three dissociation constants of the compound. Simultaneous solution for the constants was employed. The proportions of the various species in solution were calculated from the dissociation constants; differences were observed between the optimum pH for isolation of the monoanion salt in aqueous−organic systems and the value calculated from aqueous titration results. Changes in the organic content of the solvent influenced the three dissociation constants to different extents.