Idoxuridine

(Ph Eur monograph 0669)

 

C9H11IN2O5 354.1 54-42-2

 

Ph Eur


 

 

Definition

 

Idoxuridine contains not less than 98.0 per cent and not more than the equivalent of 101.0 per cent of 5-iodo-1-(2-deoxy-b-D-erythro-pentofuranosyl)pyrimidine-2,4(1H,3H)-dione, calculated with reference to the dried substance.

 

Characters

 

A white or almost white, crystalline powder, slightly soluble in water and in alcohol, practically insoluble in ether. It dissolves in dilute solutions of alkali hydroxides.

 

It melts at about 180C, with decomposition.

 

Identification

 

First identification

 

A.

 

Second identification

 

B, C, D.

 

A. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with idoxuridine CRS. Examine the substances as discs prepared using 1 mg of the substance to be examined and of the reference substance each in 0.3 g of potassium bromide R.

 

B. Examine the chromatograms obtained in the test for related substances. The principal spot in the chromatogram obtained with test solution (b) is similar in position and size to the principal spot in the chromatogram obtained with reference solution (c).

 

C. Heat about 5 mg in a test-tube over a naked flame. Violet vapour is evolved.

 

D. Disperse about 2 mg in 1 ml of water  R and add 2 ml of diphenylamine solution R2. Heat in a water-bath for 10 min. A persistent light-blue colour develops.

 

Tests

 

Solution S

 

Dissolve 0.500 g in 1M sodium hydroxide and dilute to 50.0 ml with the same solvent.

 

Appearance of solution

 

Solution S is clear  (2.2.1) and colourless (2.2.2, Method II).

 

pH (2.2.3)

 

Dissolve 0.10 g in carbon dioxide-free water  R and dilute to 100 ml with the same solvent. The pH of the solution is 5.5 to 6.5.

 

Specific optical rotation (2.2.7)

 

+28 to +32, determined on solution S and calculated with reference to the dried substance.

 

Related substances

 

Examine by thin-layer chromatography (2.2.27), using as coating substance a suitable silica gel with a fluorescent indicator having an optimal intensity at 254 nm.

 

Test solution (a)

 

Dissolve 0.20 g of the substance to be examined in a mixture of 1 volume of concentrated ammonia R and 5 volumes of methanol  R and dilute to 5 ml with the same mixture of solvents.

 

Test solution (b)

 

Dilute 1 ml of test solution (a) to 10 ml with a mixture of 1 volume of concentrated ammonia R and 5 volumes of methanol  R.

 

Reference solution (a)

 

Dissolve 20 mg of 5-iodouracil  R, 20 mg of 2¢-deoxyuridine R and 20 mg of 5-bromo-2¢-deoxyuridine R in a mixture of 1 volume of concentrated ammonia R and 5 volumes of methanol  R and dilute to 100 ml with the same mixture of solvents.

 

Reference solution (b)

 

Dissolve 0.20 g of the substance to be examined in 5 ml of reference solution (a).

 

Reference solution (c)

 

Dissolve 20 mg of idoxuridine CRS in a mixture of 1 volume of concentrated ammonia R and 5 volumes of methanol  R and dilute to 5 ml with the same mixture of solvents.

 

Reference solution (d)

 

Dilute 1 ml of test solution (b) to 20 ml with a mixture of 1 volume of concentrated ammonia R and 5 volumes of methanol  R.

 

Apply separately to the plate 5 ml of each solution. Develop twice over a path of 15 cm using a mixture of 10 volumes of concentrated ammonia R, 40 volumes of chloroform R and 50 volumes of 2-propanol  R, drying the plate in a current of cold air after each development. Examine in ultraviolet light at 254 nm. In the chromatogram obtained with test solution (a): any spots corresponding to 5-iodouracil, 2¢-deoxyuridine and 5-bromo-2¢-deoxyuridine are not more intense than the corresponding spots in the chromatogram obtained with reference solution (a) (0.5 per cent); any spot, apart from the principal spot and the spots corresponding to 5-iodouracil, 2¢-deoxyuridine and 5-bromo-2¢-deoxyuridine, is not more intense than the spot in the chromatogram obtained with reference solution (d) (0.5 per cent). The test is not valid unless the chromatogram obtained with reference solution (b) shows four clearly separated spots.

 

Iodide

 

Dissolve 0.25 g in 25 ml of 0.1M sodium hydroxide, add 5 ml of dilute hydrochloric acid R and dilute to 50 ml with water  R. Allow to stand for 10 min and filter. To 25 ml of the filtrate add 5 ml of dilute hydrogen peroxide solution R and 10 ml of chloroform R and shake. Any pink colour in the organic layer is not more intense than that in a standard prepared at the same time in the same manner using 1 ml of a 0.33 g/l solution of potassium iodide R instead of the substance to be examined (0.1 per cent).

 

Loss on drying (2.2.32)

 

Not more than 1.0 per cent, determined on 1.000 g by drying in vacuo at 60C.

 

Sulphated ash (2.4.14)

 

Not more than 0.1 per cent, determined on 1.0 g.

 

Assay

 

Dissolve 0.3000 g in 20 ml of dimethylformamide R. Titrate with 0.1M tetrabutylammonium hydroxide, determining the end-point potentiometrically (2.2.20).

 

1 ml of 0.1M tetrabutylammonium hydroxide is equivalent to 35.41 mg of C9H11IN2O5.

 

Storage

 

Store protected from light.

 

 

 


Ph Eur

 

Action and use

 

Antiviral.

 

Preparation

 

Idoxuridine Eye Drops