Analysis of the purity of cetrimide by titrations

The purity of cetrimide, trimethyl tetradecyl ammonium bromide (TTAB), which is an important preservative of many cosmetic and pharmaceutical products, was determined by three independent methods of titration. Traditionally, cetrimide was analysed by an assay method of the European Pharmacopoeia, which showed consistently a low purity of cetrimide with associated large standard deviations, however. A systematic 3% bias of the European Pharmacopoeia assay method was identified by comparing the result with results of two alternative methods of titration that exhibited high precision and high accuracy. Titration by perchloric acid showed a 99.69% ± 0.05% purity of cetrimide, and titration by silver nitrate showed a 99.85% ± 0.05% purity, while the traditional assay method predicted a purity of only 97.1% ± 0.4%. It was found that the discrepancy could be identified as differences in selectivity during the extraction step of the European Pharmacopoeia assay method. The distribution coefficients between chloroform and water of cetrimide and the corresponding iodide species (TTAI) were thus determined as 2150 ± 50 M^-1 and 68000 ± 4000 M^-1, respectively.