Acidimetry in Non-Aqueous Titrations

ACIDIMETRY IN NON-AQUEOUS TITRATIONS

In order to perform feasible titrations of weak bases, the solvent system should be selected specifically in such a fashion so as to eliminate as far as possible the competing reaction of water for the proton besides enhancing the strength of the basic species.

1. Titration of primary, secondary and tertiary amines

1.1.  Methlyldopa

In general, the reaction taking place between a primary amine and perchloric acid may be expressed as follows :

The specific reaction between methyldopa and perchloric acid is expressed by the following equation :

Materials Required : Methyldopa 0.2 g ; anhydrous formic acid : 15 ml ; glacial acetic acid : 30 ml ; dioxane : 30 ml ; 0.1 N perchloric acid and crystal violet solution.

Procedure : Weigh accurately about 0.2 g and dissolve in 15 ml of anhydrous formic acid, 30 ml of glacial acetic acid and 30 ml of dioxane. Add 0.1 ml of crystal violet solution and titrate with 0.1 N perchloric acid. Perform a blank determination and make any necessary correction. Each ml of 0.1 N perchloric acid is equivalent to 0.02112 g of C₁₀H₁₃NO₄.

Calculations : The percentage of methyldopa present in the sample is given by :

1.2.  Methacholine Clloride

Materials Required : Methacholine chloride : 0.4 g ; glacial acetic acid : 50 ml ; mercuric acetate solution : 10 ml ; 0.1 N perchloric acid and crystal violet solution.

Procedure : Weigh accurately about 0.4 g, previously dried and stored in a vacuum desiccator, and dissolve in 50 ml of glacial acetic acid, add 10 ml of mercuric acetate solution, one drop of crystal violet solution and titrate with 0.1 N perchloric acid to a blue-green end point. Perform a blank determination and make any necessary correction. Each ml of 0.1 N perchloric acid is equivalent to 0.01957 g of C₈H_l8ClNO₂.

Equation :

Mercuric acetate : It is essentially added to prevent the interference of the hydrochloric acid dis-placed through the formation of the relatively un-ionized HgCl₂, thereby making a predominant shift in the equilibrium so that the titrimetric reaction is quantitative.

Blank Titration : It is usually carried out to account for the possible reaction of atmospheric moisture with the titrant perchloric acid and also to check the titrant being employed to bring about the blue-green end-point.

Calculations : The percentage of methacholine chloride in the sample may be calculated by the following expression :

1.3.  Cognate Assays

Table 5.1, enlists the various cognate determinations using different indicators but employing the same titrant i.e., 0.1 N perchloric acid.

1.4.  Potentiometric Titrations

These non-aqueous titrations may also be carried out with the help of potentiometric titrations which technique shall be discussed at length elsewhere in this book.

It is always preferred to first ascertain the equivalence point of a given neutralization reaction potentiometrically (i.e., an instrumental method of analysis) ; and secondly, by selecting an appropriate indicator that will ensure the sharpest colour change for the least increment of volume of titrant added near the equivalence point.

In actual practice, however, there are quite a number of non-aqueous titrations of pharmaceutical substances either in pure or in dosage forms that can be successfully performed potentiometrically.

2. Titration of Halogen Acid Salts of Bases

In general, the halide ions, namely : chloride, bromide and iodide are very weakly basic in character so much so that they cannot react quantitatively with acetous perchloric acid. In order to overcome this problem, mercuric acetate is usually added (it remains undissociated in acetic acid solution) to a halide salt thereby causing the replacement of halide ion by an equivalent amount of acetate ion, which serves as a strong base in acetic acid as shown below :

2.A. Amitriptyline Hydrochloride

Materials Required : Amitriptyline hydrochloride : 1.0 g ; mercuric acetate ; crystal violet ; 0.1 N perchloric acid ; glacial acetic acid.

Procedure : Weigh accurately about 1.0 g and dissolve in 50 ml of glacial acetic acid, warming slightly, if necessary, to affect the solution. Cool, add 10 ml of mercuric acetate solution, two drops of crystal violet solution and titrate with 0.1 N perchloric acid to a green end-point. Perform a blank determination and make any necessary correction. Each ml of 0.1 N perchloric acid is equivalent to 0.03139 g of C₂₀H₂₃N. HCl.

Equations :

Calculations :

3. Cognate Assays

The following estimations of various pharmaceutical substances can also be carried out by the aforesaid procedure (Table 5.3) :