Iodometric Assays

IODOMETRIC ASSAYS

In iodometric determinations the pharmaceutical substance oxidizes KI in an acidic medium to produce an equivalent quantity of iodine that may be assayed by titration with a standard solution of sodium thiosulphate.

1. Chlorinated Lime

Chlorinated lime or bleaching powder, CaOCl₂, contains about 30% w/w of available chlorine.

Theory : Chlorinated lime reacts with acetic acid to produce a mole each of calcium acetate, hydro-chloric acid and hydrochlorous acid. The two acids interact to give water and chlorine, and the latter reacts with HI to liberate iodine that can be estimated by titrating with 0.1 N sodium thiosulphate solution. The various reactions involved may be expressed as given below :

Materials Required : Chlorinated lime : 4 g ; dilute acetic acid : 5 ml ; potassium iodide : 3 g ; acetic acid : 5 ml ; 0.1 N sodium thiosulphate solution.

Procedure : Weigh accurately 4.0 g of chlorinated lime and triturate it in a glass-pestle-mortar with a little DW. Transfer the paste quantitatively into a 1 litre volumetric flask and shake thoroughly. Take a 100 ml volumetric flask, rinse it with a small quantity of the suspension from the 1 litre flask and finally fill it up with the suspension. Rinse out a 250 ml iodine flask containing a little dilute acetic acid and a little of the suspension from the 1-litre flask in order to oxidise any inorganic substance present in the iodine flask. Finally, wash it thoroughly with DW. Now, transfer 100 ml of the suspension completely from the 100 ml volumetric flask to the iodine flask by washing the former repeatedly with DW. Add to it acetic acid 5 ml followed by KI 3.0 g and shake the contents of the flask thoroughly. Titrate the liberated iodine with 0.1 N sodium thiosulphate which is equivalent to 0.003546 g of chlorine.

From this value the percentage of chlorine present in the given sample of chlorinated lime can be calculated.

2. Ferric Ammonium Citrate

Theory : In ferric ammonium citrate it is taken for granted that the entire iron is oxidized to the Fe²⁺ state and practically little Fe²⁺ is present. Thus, the ferric ion present in a known amount of the sample liberates an equivalent amount of iodine from an acidified KI solution. Thus, we have :

Materials Required : Ferric ammonium citrate : 0.5 g ; sulphuric acid conc. : 1 ml ; 0.1 N KMnO₄ solution : 50 ml ; hydrochloric acid : 15 ml ; potassium iodide : 2.0 g ; 0.1 N sodium thiosulphate.

Procedure : Weigh accurately about 0.5 g of ferric ammonium citrate and dissolve the sample in 15 ml DW. Add to it slowly 1 ml of sulphuric acid and warm gently to attain a yellow colouration so as to decompose the iron and ammonium citrate complex completely. Cool and add 0.1 N potassium permanganate solution dropwise from a burette to obtain a pink colour that persists for 5 seconds. To the resulting solution add hydrochloric acid 15 ml and potassium iodide 2.0 g, shake well and set aside for 3 minutes so that iodine may be liberated completely. Now, add 60 ml of water and titrate with 0.1 N sodium thiosulphate solution while shaking the contents continuously till a colourless end-point is achieved.

Precautions :

(i) Addition of excess of KMnO₄ solution must be avoided, since pink colour developed shall disap-pear within a short span, which may ultimately give false high results,

(ii) Washing down during the course of titration must be checked rigidly in order to maintain the right proportion of various substances in the solution,

(iii) End-point is almost colourless, hence starch indicator can be skipped totally, and

(iv) KMnO₄ oxidizes the traces of Fe²⁺ to Fe³⁺ in the sample, if any.

3. Thyroid

Thyroxine and diidotyrosine are the two iodine-substituted organic compounds which essentially con-stitute the active principles present in dried thyroid gland. The latter on being subjected to pyrolysis with anhydrous K₂CO₃, gives rise to an equivalent amount of KI present in the sample. Soon after the completion of carbonization, the crucible is cooled and the residue is extracted with water to dissolve KI, carbonates and other soluble compounds. The resulting solution is filtered and treated with Br₂ in the presence of phosphoric acid (H₃PO₄) so that complete oxidation of iodide to iodate is caused. The following reaction takes place :

The excess of bromine is removed by warming the acidic solution gently till the vapours show a negative test with starch-iodide paper. However, the residual traces of Br₂ are reduced by treatment of the resulting solution with phenol to yield the corresponding 2,4,6-tribromophenol as shown below :

Lastly, iodate (IO₃^–) in a weak acidic medium quantitatively oxidizes KI to an equivalent amount of iodine, as expressed below :

It is evident from the above equation that each gram-atomic weight of iodine in thyroid is converted to 1 mol of iodate and finally to 3 mol or 6 equivalent of iodine. Therefore, the equivalent weight of the iodine present in the dried thyroid gland is 21.15 g (i.e., 1/6 × 127 At. wt. of I ₂). Hence, each millilitre of 0.01 N sodium thiosulphate is equivalent to 0.0002115 g of iodine (i.e., 0.01 × 0.02115 g).

Materials Required : Thyroid gland dried 1.0 g ; anhydrous potassium carbonate : 17.0 g ; bromine solution (9.6 ml of Br₂ and 30 g of KBr in 100 ml DW) : 7.0 ml ; dilute phosphoric acid (10% w/v) : 42.0 ml ; starch iodide paper ; phenol solution (saturated solution of phenol in water) : 5.0 ml ; potassium iodide solution (10% w/v in water) ; 0.01 N sodium thiosulphate solution ; starch solution.

Procedure : Weigh accurately about 1.0 g of dried thyroid gland in a porcelain crucible, add 7.0 g of anhydrous K₂CO₃, mix thoroughly and overlay with further 10 g more of anhydrous K₂CO₃, finally compact the mixture by tapping gently. Incenerate for 25 minutes at 675°—700°C in a preheated muffle furnace. Cool the contents, add 20 ml of DW, boil gently and decant through a filter paper into a flask. Repeat the extraction by boiling with 20 ml DW, wash the crucible and the residue on the filter with hot water until the filtrate is about 200 ml. To it add 7.0 ml of freshly prepared bromine solution followed by 40 ml of dilute phosphoric acid and continue boiling slowly till starch iodide paper is no longer coloured blue by the vapours. While boiling is in progress top up the volume to 200 ml by adding DW at intervals. Cool and add 5 ml of phenol solution and allow to stand for 5 minutes. Add 2 ml of dilute phosphoric acid and 5 ml of potassium iodide solution and titrate immediately with 0.01 N sodium thiosulphate solution employing starch solution as indi-cator towards the end-point. A blank estimation is also carried out simultaneously and necessary correction incorporated. Each ml 0.1 N sodium thiosulphate is equivalent to 0.0002115 g of I.

Precautions :

(i) Potassium carbonate should be perfectly anhydrous otherwise decrepitation would take place caus-ing loss of material during pyrolysis,

(ii) Both the temperature of the muffle furnace and the extent of heating should be monitored closely, because KI is significantly volatile at an elevated temperature and part of it may be lost due to extended heating, and

(iii) The solution from which excess Br₂ is removed by heating must be acidic, otherwise a portion of Br₂ shall be fixed in the form of potassium hypobromite (KBrO).

4. Cognate Assays

A few pharmaceutical substances can be assayed by titrating the liberated iodine from potassium iodide with sodium thiosulphate as stated in Table 7.3.