भारतीय भेषज संहिता आयोग
Pentoxifylline
C13H18N4O3 Mol. Wt. 278.3
Pentoxifylline is 1 H-purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-1-(5-oxohexyl).
Pentoxifylline contains not less than 98.0 per cent and not more than 102.0 per cent of C13H18N4O3,.
Category. Vasodilator; antihypertensive.
Description. A white to almost white crystalline powder.
Identification
- Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained withpentoxifylline RSor with the reference spectrum of pentoxifylline.
In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution (b).
Tests
Appearance of solution. A 2.0 per cent w/v solution in carbon dioxide-free water, is clear and colourless (2.4.1).
Acidity. A 2.0 per cent w/v solution in carbon dioxide free water, add 1 drop of bromothymol blue solution.
Not more than 0.2 ml of 0.01 M sodium hydroxide is required to produce a colour change to blue.
Related substances. Determine by liquid chromatography (2.4.14), as described under Assay with the following modifications.
Test solution. Dissolve 35 mg of the substance under examination in the mobile phase and dilute to 100.0 ml with the mobile phase.
Reference solution (a). A 0.00007 per cent w/v solution of caffeine and 0.035 per cent w/v solution of pentoxifylline RS in the mobile phase.
Reference solution (b). A 0.00007 per cent w/v solution of pentoxifylline RS in the mobile phase.
Chromatographic system
– injection volume: 20 µl.
Inject reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to caffeine and pentoxyfylline is not less than 10 obtained with reference solution (a) and the relative standard deviation for replicate injections is not more than 5.0 obtained with reference solution (b).
Inject reference solution (b) and the test solution. Run the chromatogram not less than 5 times the principal peak. In the chromatogram obtained with the test solution, the area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent). The sum of areas of all the secondary peaks is not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent).
Chlorides. Dissolve 2.0 g of the substance under examination in 30 to 40 ml of water, if necessary neutralize the solution with nitric acid to litmus. Add 1 ml of each of nitric acid and of silver nitrate solution and dilute to 50.0 ml with water. Mix, and allow to stand for 5 minutes protected from direct sunlight. Compare the turbidity, if any, The resulting solution shows no more chloride than corresponds to 0.31 ml of 0.02 M hydrochloric acid. (110 ppm). 2.5 g sample complies with the limit test for chlorides (100 ppm).
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Sulphate. Dissolve 1.0 g of the substance under examination in 30 to 40 ml of water, if necessary neutralize the solution with hydrochloric acid to litmus. Add 1 ml of 3 M hydrochloric acid, 3 ml of barium chloride solution and dilute to 50.0 ml with water. Mix, and allow to stand for 10 minutes protected from direct sunlight. Compare the turbidity. The resulting solution shows no more sulphate than corresponds to 0.2 ml of 0.01 M sulphuric acid. (200 ppm). 0.75 g sample complies with the limit test for sulphates (200 ppm).
Heavy Metals (2.3.13). 2.0 g complies with the limit test for heavy metals, method B (10 ppm).
Loss on drying (2.4.19). Not more than 0.5 per cent, by drying under vaccum at 60° for 3 h.
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 50 mg of the substance under examination in 100 ml of the mobile phase and dilute
1.0 ml of the solution to 10.0 ml with the mobile phase.
Reference solution (a). A 0.0024 per cent w/v solution of caffeine and 0.0048 per cent w/v solution of pentoxifylline RS in the mobile phase.
Reference solution (b). A 0.005 per cent w/v solution of pentoxifylline RS in the mobile phase.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm)
– mobile phase: a mixture of 2 volumes of methanol, 2.5 volumes of tetrahydrofuran, 15 volume of acetonitrile and 80 volumes of 0.1 per cent w/v solution of perchloric acid.
– flow rate: 0.7 ml per minute,
– spectrophotometer set at 273 nm,
– injection volume: 10 µl.
Inject reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to caffeine and pentoxyfylline is not less than 10 obtained with reference solution (a) and the relative standard deviation for replicate injections is not more than 2.0 obtained with reference solution (b).
Inject reference solution (b) and the test solution.
Calculate the content of C13H18N4O3.
Storage: Store protected from moisture.
