Argentometric Precipitation Methods: Assay Methods

ASSAY METHODS

Argentometric titrations may be divided into two broad categories, namely :

(i) Direct titration with silver-nitrate, and

(ii) Ammonium thiocyanate-silver nitrate titrations (Volhard’s Method).

1. DIRECT TITRATION WITH SILVER NITRATE

Pharmaceutical substances essentially containing halides may be estimated by direct titration with silver nitrate solution as a titrant.

1.1 Preparation of 0.1 N Silver Nitrate Solution

Materials Required : Silver nitrate (AR) : 16.989 g.

Procedure : Weigh accurately 16.989 g of silver nitrate on a watch-glass and transfer quantitatively into a 1 litre volumetric flask. Add freshly prepared DW and make up the volume to 1000 ml. Thus, we have :

1.2. Standardization of 0.1 N Silver Nitrate Solution

Materials Required : Sodium chloride : 0.1 g ; acetic acid (33% w/v) : 5 ml ; methyl alcohol (95%) : 50 ml ; eosin solution (0.5% w/v in water) : 5 ml ; 0.1 N silver nitrate solution.

Procedure : Weigh accurately about 0.1 g of sodium chloride, previously dried at 110°C for 2 hours, and dissolve in 5 ml of water. Add 5 ml of acetic acid, 50 ml of methyl alcohol and three drops of eosin solution. Stir thoroughly on a magnetic stirrer and titrate with the silver nitrate solution till the white particles of AgCl change from white to pink. Each 0.005844 g of sodium chloride is equivalent to 1 ml of 0.1 N silver nitrate.

1.2.1.  Potassium Chlroride

Materials Required : Potassium chloride : 0.25 g ; potassium chromate solution (5% w/v in water) : 10 ml ; 0.1 N silver nitrate solution.

Procedure : Weigh accurately about 0.25 g of potassium chloride in a conical flask and dissolve it in 50 ml of DW and titrate with 0.1 N silver nitrate solution, using 2-3 drops of potassium chromate solution as indicator till precipitation of red chromate is indicated. Each ml of 0.1 N silver nitrate solution is equivalent to 0.007455 g of KCl.

Equations :

1.2.2. Chloral Hydrate

Materials Required : Chloral hydrate : 4.0 g ; sodium hydroxide (N) : 30 ml ; sulphuric acid (N) ; phenolphthalein solution (1.0% w/v in 50% v/v alcohol) ; 0.1 N silver nitrate solution ; potassium chromate solution (5% w/v in water).

Procedure : Weigh accurately about 4 g of chloral hydrate and dissolve in 10 ml of DW and add 30 ml of N sodium hydroxide solution. Allow the resulting mixture to stand for 2 minutes, and then titrate with N sulphuric acid, employing phenolphthalein solution as indicator till a colour change from pink to colourless is achieved. Titrate the neutralized liquid thus obtained with 0.1 N silver nitrate using potassium chromate solution as indicator till precipitation of red chromate is obtained, Add, now 2/15th of the amount of 0.1 N silver nitrate used to the amount of N sulphuric acid used in the first titration and deduct the figure so obtained from the amount of N sodium hydroxide added. Each ml of N sodium hydroxide, obtained as difference, is equivalent to 0.1654 g of C₂H₃Cl₃O₂.

Explanation :

(i) The estimation depends upon the interaction between chloral hydrate and sodium hydroxide as shown by the following equation :

(ii) As the chloroform generated in Eq. (a) undergoes chemical reaction with the alkali to a certain degree; therefore, addition of alkali followed by back titration does not afford the correct assay. Thus, we have :

(iii) The ionized chloride generated from the additional side reaction (b) may be estimated by titration with 0.1 N silver nitrate solution, and necessarily a correction has got to be made to the alkali-titration reading so as to adequately compensate for this side reaction. Thus, from equation (b) we have :

Therefore, it is evident that 2/15th of the volume of 0.1 N AgNO₃ (i.e., 2/15th of 30,000 = 4,000) needed shall give the volume of N NaOH that reacted with chloroform as per Eq. (b).

1.2. Cognate Assays

The pharmaceutical substances in Table 8.1, can be assayed by direct titration with silver nitrate using a suitable indicator.

2. AMMONIUM THIOCYANATE-SILVER NITRATE TITRATIONS (VOLHARD’S METHOD)

Volhard’s method is based on two major aspects, namely :

(a) Complete precipitation of insoluble silver salts from nitric acid solution by adding an excess of silver nitrate solution to a corresponding soluble salt, and

(b) Estimation of excess of silver nitrate solution by carrying out residual titration with standard am-monium thiocyanate solution, employing ferric ammonium sulphate as an indicator.

Thus, ammonium thiocyanate reacts with silver nitrate in nitric acid solution as below :

NH₄SCN + AgNO₃ → AgSCN ↓ + NH₄NO₃

However, in actual practice the thiocyanate solution is always taken in the burette and is run directly into the silver nitrate solution in the flask that has been duly acidified with nitric acid. Ferric ammonium sulphate is the choicest indicator since the end point is visibly detected by a deep red colour (ferric thiocyanate) due to the interaction of Fe²⁺ ions with a trace of SCN^– ion.

Precautions :

(i) Nitric acid must be free from nitrous acid, otherwise thiocyanic acid may give an instant red colouration, and

(ii) Temperature of the solution should be maintained below 25°C since at an elevated temperature the red colour of the ferric thiocyanate complex fades away rapidly. Therefore, we have :

NH₄SCN ≡ AgNO₃ ≡ H

2.1. Preparation of 0.1 N Ammonium Thiocyanate Solution

Materials Required : Ammonium thiocyanate : 8.0 g.

Procedure : Weigh about 8.0 g of ammonium thiocyanate and transfer it quantitatively in 1 litre volu-metric flask. Dissolve it in DW and make up the volume upto the mark.

Equation :

2.2. Standardization of 0.1 N Ammonium Thiocyanate Solution

Materials Required : 0.1 N Silver nitrate solution : 25 ml ; nitric acid (16 N) : 2 ml ; ferric ammonium sulphate (10% w/v in water) : 2 ml ; 0.1 N ammonium thiocyanate solution.

Procedure : Pipette 25 ml of a standard 0.1 N AgNO₃ solution into a glass-stoppered flask (iodine-flask), dilute with 50 ml of DW, add to it 2 ml of nitric acid and 2 ml of ferric ammonium sulphate solution and titrate with ammonium solution to the first appearance of red-brown colour. Each ml of 0.1 N silver nitrate is equivalent to 0.007612 g of NH₄SCN.

Note : Soon after the addition of ammonium thiocyanate a white precipitate of silver thiocyanate is formed first and then a reddish-brown colour appears that fades out completely upon shaking thereby leaving a white precipitate of silver thiocyanate. The end-point is indicated by the appearance of a permanent faint reddish brown colour that does not vanish upon shaking.

2.2.1.  Chlorobutol

Materials Required : Chlorobutol : 0.2 g ; alcohol (95%) : 5 ml ; sodium hydroxide solution (20% w/v in water) : 5 ml ; nitric acid (16 N) : 5 ml ; nitrobenzene : 1 ml ; 0.1 N silver nitrate solution : 50 ml ; ferric ammonium sulphate solution (10% w/v in water) ; 0.1 N ammonium thiocyanate solution.

Procedure : Weigh accurately about 0.2 g of chlorobutol in a flask and dissolve in 5 ml of alcohol. Add to it 5 ml of sodium hydroxide solution, and boil under a reflux condenser for 15 minutes. Cool, dilute with 20 ml of DW, add 5 ml of nitric acid, 1 ml of nitrobenzene and 50 ml of 0.1 N silver nitrate solution. Shake the contents vigorously for 1 minute, add 4 ml of ferric ammonium sulphate solution and titrate the excess of silver nitrate with 0.1 N ammonium thiocyanate solution. Each ml of 0.1 N silver nitrate is equivalent to 0.005917 g of C₄H₇Cl₃O.

Explanation : Chlorine combined originally to chlorobutol is being converted by hydrolysis in the presence of sodium hydroxide to ionic chloride that may be estimated quantitatively by Volhard’s method in the presence of nitrobenzene.

Thus, we have :

2.2.2.  Ethionamide

Theory : Theoretically the cleavage of thioamide link in ethionamide takes place in an acidic medium. Subsequent neutralization with NH₄OH yields ammonium sulphide which on addition of silver nitrate yields a precipitate of Ag₂S. Thus we have :

Materials Required : Ethionamide : 0.3 g ; dilute sulphuric acid (10% w/w) : 10 ml ; dilute ammonia solution (4.25 ml of strong ammonia solution in 100 ml of water) ; 0.1 N silver nitrate : 50 ml ; dilute nitric acid (10.6 ml of nitric acid to 100 ml of water) : 60 ml ; ferric ammonium sulphate solution (10% w/v in water) : 5 ml ; and 0.1 N ammonium thiocyanate solution.

Procedure : Weigh accurately about 0.3 g of ethionamide in a flask and dissolve in 10 ml of dilute sulphuric acid. Add to it 100 ml of water, 20 ml of dilute ammonia solution and rapidly 50 ml of 0.1 N silver nitrate solution. Allow the resulting mixture to stand for a few minutes, filter and wash the filter paper with three successive quantities, each of 10 ml of DW. To the combined filtrate and washings, add 60 ml of dilute nitric acid, cool and titrate with 0.1 N ammonium thiocyanate employing 5 ml of ferric ammonium sulphate solution as an indicator. Each ml of 0.1 N silver nitrate is equivalent to 0.008312 g of C₈H₁₀N₂S.

2.2.3. Cognate Assays

A good number of pharmaceutical substances can be assayed by Volhard’s method and are mentioned in Table 8.2.