Applications of Potentiometric Titrations in Pharmaceutical Analysis

APPLICATIONS OF POTENTIOMETRIC TITRATIONS IN PHARMACEUTICAL ANALYSIS

Potentiometric titrations have been used extensively for assay of a number of official compounds. A few typical examples would be described here, namely : Nitrazepam ; Allopurinol ; and Chloridine hydrochloride.

A. Assay of Nitrazepam :

Materials Required : Nitrazepam : 0.25 g ; acetic anhydride : 25.0 ml ; perchloric acid (0.1 M) : 250 ml ; a Potentiometer ; a Magnetic Stirrer ; Burette (50 ml) ;

Theory : Nitrazepam is a weakly basic compound and hence, it may be titrated conveniently by means of a non-aqueous titration technique and determining the end-point potentiometrically.

Procedure : Weigh accurately 0.25 g of nitrazepam and dissolve in 25.0 ml of acetic anhydride. Titrate with 0.1 M perchloric acid placed in a burette and adding it carefully into the beaker kept on a magnetic stirrer potentiometrically. Each ml of 0.1 M perchloric acid is equivalent to 28.13 mg of C₁₅H₁₁N₃O₃.

B. Assay of Allopurinol :

Materials Required : Allopurinol : 0.12 g ; dimethylformamide : 100.0 ml ; tetrabutylammonium hydroxide (0.1 M) : 1 L ;

Preparation of 0.1 M Tetrabutylammonium hydroxide (1 Litre) : Dissolve 40 g of tetrabutylammonium iodide in 90 ml of anhydrous methanol, add 20 g of finely powdered silver oxide and shake vigorously for 1 hour. Centrifuge a few ml of the mixture and test the supernatant liquid for iodides. If a positive reaction is obtained add a further 2 g of silver oxide and shake for 30 minutes. Repeat this procedure until the mixture is free from iodides, filter through a fine sintered-glass filter and wash the reaction vessel and filter with three 50-ml quantities of toluene. Add the washings to the filtrate and add sufficient toluene to produce 1000 ml. Pass dry carbon-dioxide free N₂ through the solution for 5 minutes.

Standardization of 0.1 M Tetrabutylammonium Hydroxide : To 10 ml of dimethylformamide add 0.05 ml of a 0.3 % w/v solution of thymol blue in methanol and titrate with the tetrabutylammonium hydroxide solution until a pure blue colour is produced. Immediately add 0.2 g of benzoic acid, stir to effect solution and titrate with the tetrabutylammonium hydroxide solution until the pure blue colour is restored. Protect the solution from atmospheric CO₂ throughout the titration. The volume of titrant used in the second titration represents the amount of tetrabutylammonium hydroxide required. Each ml of 0.1 M tetrabutylammonium hydroxide Vs is equivalent to 12.21 mg of C₇H₆O₂.

Procedure : Dissolve 0.12 g of accurately weighed allopurinol in 50 ml of dimethylformamide, with gentle heating, if necessary. Titrate to the colour change of the indicator that corresponds to the maximum absolute value of dE/dV in a potentiometric titration (where E is the electromnotive force and V is the volume of the titrant). Each ml of 0.1 M tetrabutylammonium hydroxide Vs is equivalent to 13.61 mg of C₅H₄N₄O.

C. Clonidine Hydrochloride :

Materials Required : Clonidine hydrochloride : 0.2 g ; ethanol (96%) : 100 ml ; 0.1 M ethanolic sodium hydroxide Vs : 1 L (Add 3.3 g of 10 M sodium hydroxide solution to 250 ml of absolute ethanol).

Standardization of 0.1 M Ethanolic Sodium Hydroxide Solution Vs : Dissolve 0.2 g of benzoic acid in a mixture of 10 ml of ethanol (96%) and 2 ml of water and titrate with the ethanolic sodium hydroxide solution using 0.2 ml of thymolphthalein solution (a 0.1 % w/v solution of thymolphthalein in ethanol (96%) as indicator. Each ml of 0.1 M ethanolic sodium hydroxide Vs is equivalent to 12.21 mg of C₇H₆O₂.

Procedure : Dissolve 0.2 g of clonidine hydrochloride in 70 ml of ethanol (96%) and titrate with 0.1M ethanolic sodium hydroxide Vs determining the end-point potentiometrically. Each ml of 0.1 M ethanolic sodium hydroxide Vs is equivalent to 26.66 mg of C₉H₉Cl₂,N₃, HCl.

1. COGNATE ASSAYS

A plethora of official drugs are assayed by the potentiometric method in various official compendia, and a few selected examples are given in Table 16.3, which may be assayed potentiometrically :