Granisetron Tablets
Granisetron Hydrochloride Tablets
Granisetron Hydrochloride Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of granisetron, C18H24N4O.
Usual strengths. 1 mg; 2 mg.
Identification
- Determine by thin-layer chromatography (2.4.17), coating the plate withsilica gelGF254.
Mobile phase. A mixture of 60 volumes of methylene chloride, 40 volumes of alcohol, 5 volumes of water and
2 volumes of ammonium hydroxide.
Test solution. Disperse a quantity of the powdered tablets containing 4 mg of Granisetron Hydrochloride with 10 ml of 0.1 M hydrochloric acid and sonicate.
Reference solution. A 0.044 per cent w/v solution of granisetron hydrochloride RS in 0.1 M hydrochloric acid.
Apply to the plate 20 µl of each solution. After development, dry the plate in a current of air and examine under ultraviolet light at 254 nm. The principal spot in the chromatogram obtained with the test solution corresponds to the principal spot in the chromatogram obtained with reference solution.
- In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with reference solution (a).
Tests
Dissolution (2.5.2).
Apparatus No. 1,
Medium. 500 ml of a phosphate buffer, prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate in 800 ml of water, adjusting the pH to 6.5 with 1 N sodium hydroxide and diluting to 1000 ml with water.
Speed and time. 50 rpm and 30 minutes.
Withdraw a suitable volume of the medium and filter.
Determine by liquid chromatography (2.4.14).
note: Perform the determination under subdued light and use amber autosampler vials and low-actinic glassware.
Buffer solution— Dissolve 15.6 g of monobasic sodium phosphate dihydrate in 900 ml of water, adjust to pH 2.0 with orthophosphoric acid, and dilute with water to 1000 ml.
Test solution. Dilute the filtrate, if necessary, with the buffer solution.
Reference solution. Dissolve a quantity of granisetron hydrochloride RS in the buffer solution to obtain a solution of known concentration similar to the test solution.
Chromatographic system
– a stainless steel column 15 cm × 4.6 mm, polar end-capped packed with octadecylsilane bonded to porous silica (4 µm),
– mobile phase: a mixture of 75 volumes of buffer solution, 24 volumes of methanol and 1.1 volume of tetrahydrofuran,
– flow rate: 1.2 ml per minute,
– spectrophotometer set at 300 nm,
– injection volume: 100 µl.
Inject the reference solution and the test solution.
- Not less than 75 per cent of the stated amount ofC18H24N4O.
Related substances. Determine by liquid chromatography (2.4.14).
note: Perform the determination under subdued light and use amber autosampler vials and low-actinic glassware.
Buffer solution— Dissolve 15.6 g of monobasic sodium phosphate dihydrate in 900 ml of water, adjust to pH 2.0 with orthophosphoric acid, and dilute with water to 1000 ml.
Test solution. Weigh and powder 20 tablets. Weigh and transfer a quantity of powder containing 10 mg of granisetron in 100.0 ml volumetric flask, add about 50 ml of buffer solution and disperse with the aid of ultrasound for about 10 minutes, cool and dilute to volume with buffer solution and filter.
Reference solution (a). A 0.011 per cent w/v solution of granisetron hydrochloride RS in buffer solution.
Reference solution (b). A solution containing 0.01 per cent w/v of granisetron hydrochloride RS and 0.001 per cent w/v of each granisetron impurity B, C and D in the buffer solution.
Chromatographic system
– a stainless steel column 15 cm × 4.6 mm, polar end-capped packed with octadecylsilane bonded to porous silica (4 µm),
– mobile phase: a mixture of 75 volumes of buffer solution, 24 volumes of methanol and 1.1 volume of tetrahydrofuran,
– flow rate: 1.2 ml per minute,
– spectrophotometer set at 300 nm,
– injection volume: 20 µl.
Name Relative Correction
retention time factor
Granisetron impurity A1 0.5 to 0.6 ---
Granisetron impurity B2 0.7 1.25
Granisetron (Retention time:
about 7.0 minutes) 1.0 ---
Granisetron impurity C3 1.2 1.0
Granisetron impurity D4 2.1 to 2.3 0.67
1 2-methyl-N-[(1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-2H-indazole-3-carboxamide,
2 N-[(1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide,
3 N-[(1R,3r,5S)-9-azabicyclo[3.3.1]non-3-yl]-1-methyl-1H-indazole-3-carboxamide,
4 1-methyl-1H-indazole-3-carboxylic acid,
Inject reference solution (b). The test is not valid unless the resolution between the peaks corresponding to impurity C and granisetron is not less than 2, the tailing factor is not less than 0.8 and not more than 1.5.
Inject reference solution (a) and the test solution. In the chromatogram obtained with the test solution, the area of peak corresponding to impurity C is not more than 0.007 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.7 per cent). The sum of areas of all the known impurities peaks is not more than 0.013 times the area of the principal peak in the chromatogram obtained with reference solution (a) (1.3 per cent). Other secondary peak is not more than 0.005 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent). Ignore any peak with relative retention time about 0.5 to 0.6 for granisetron impurity A. Ignore any peak with an area less than 0.01 times of the peak obtained from reference solution (a) (0.1 per cent).
Uniformity of content. Determine by liquid chromatography (2.4.14). as described under related substances with the following modification.
Test solution. Disperse 1 tablet in the buffer solution with the aid of ultrasound, and dilute as necessary to obtain a solution containing 0.01 per cent w/v solution of Granisetron.
Inject the test solution and reference solution (a).
Calculate the content of C18H24N4O in the tablets.
Other tests. Comply with the tests stated under Tablets.
Assay. Determine by liquid chromatography (2.4.14), as described under related substances with the following modification.
Inject the test solution and reference solution (a).
Calculate the content of C18H24N4O in the tablets.
Storage. Store protected from light and moisture, at a temperature below 300.
Labelling. The label states the strength in terms of the equivalent amount of Granisetron.