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.
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.
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.
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.
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 :