Non-Aqueous Titrations

NON-AQUEOUS TITRATIONS

INTRODUCTION

During the past four decades a plethora of newer complex organic medicinal compounds have taken cognizance in the therapeutic armamentarium. Evidently, these compounds posed two vital problems of quality control, both in pure and dosage forms by virtue of their inherent characteristics, namely :

(a) poor solubility, and

(b) weak reactivity in aqueous medium.

Initially, the above two problems were usually circumvented in the following manner :

Example 1 : Amine salts—It is first changed to the water-soluble free base, extracted with an appro-priate organic solvent and treated with an excess volume of standard acid ; subsequently, the solvent was evaporated, and the remaining acid determined with a standard base.

Example 2 : Sodium salts—It is first acidified to release the water-insoluble organic acid, extracted with a suitable organic solvent, the solvent was removed and the residue was subsequently dried and weighed.

Example 3 : Nitrogen containing compounds—They are estimated by micro Kjeldahl’s Method. Nevertheless, such specific quantitative methods gave rise to certain serious anomalies and drawbacks.

In order to overcome these shortcomings the non-aqueous titrations were introduced.

Non-aqueous titrations have the following advantages, namely :

·              Elimination of poor solubility of substances,

·              Enhancement of weak reactivity of substances,

·              Selective titration by using suitable solvent and titrant of acidic/basic components of physiologi-cally active moiety of a salt,

·              Maintenance of speed, precision, accuracy and simplicity at par with classical methods of analysis, and

·              Weak bases which have Kb values less than 10^–6 can be titrated satisfactorily by non-aqueous titrations. The reason being that in aqueous medium and at higher Kb values (> 10^–6) the solvent water competes progressively with the basic species in solution for the proton of the solvent.