Stepwise Determination of Quaternary Ammonium Salts and Aromatic Amines in Pharmaceuticals by Ion Association Titration

A stepwise titrimetric method has been developed for the simultaneous determination of pharmaceutical quaternary ammonium salts (R4N+) and aromatic amines (R3N). The method is based on the solvent extraction of R4N+ and R3NH+ with an ion association reagent. Sodium tetrakis(4-fluorophenyl)borate and sodium tetraphenylborate were used as titrants and potassium tetrabromophenolphthalein ethyl ester (TBPE) was used as an indicator. The ion associate which formed between R4N+ ion and TBPE made a blue color in 1,2-dichloroethane, while the ion associate formed between R3NH+ and TBPE showed a red-violet one. Sample solutions containing quaternary ammonium and/or amine compounds were titrated with sodium tetrakis(4-fluorophenyl)borate or sodium tetraphenylborate. When one drop of excess titrant was added, the color of the organic phase turned from blue or red-violet to yellow at the equivalence point. On the other hand, in the mixture of R4N+ and R3N, the color changed from blue to red-violet at the first equivalence point, and then its color turned to yellow at the second equivalence point. The quaternary ammonium compound and aromatic amine in pharmaceuticals could be simultaneously and successfully determined by the proposed titration method.