Measure of alkalinity in an alcohol/water mixture by potentiometric end-point detection. Critical remarks on a new method in the European pharmacopoeia

摘要

The European Pharmacopoeia introduced a new alkalimetric method for assay of alkaloid (and other N-base) salts. The principle of method is: after preliminary addition of small amount of hydrochloric acid, titration is carried out with 0.1 N NaOH in alcohol/water mixture with potentiometric end-point detection. The applicability and reproducibility of this method have been examined at 11 substances. The results of alkalimetric method were compared to those obtained by nonaqueous titration (Ph. Hg. VII.). The method of Ph. Eur. is well reproducible (SD < +/- 0.50), however it could not be applied in case of some compounds (4 cases out of 11). Authors revealed that for the titration carried out according to the present prescription of Ph. Eur. 4., minimum pKa 7 should be the basicity of the alkaloids. They suggest to perform the titration in 70% alcohol and without preliminary addition of HCl for weaker bases.