Ropinirole Tablets
Ropinirole Hydrochloride Tablets
Ropinirole Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of ropinirole, C18H24N4O.
Usual strengths. 0.25 mg; 0.5 mg; 1 mg; 2 mg; 4 mg; 5 mg.
Identification
- 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. 2,
Medium. 500 ml of a buffer solution, prepared by dissolving 2.9 g of sodium citrate dihydrate and 3.3 g of anhydrous citric acid in 1000 ml of water, pH 4.0.
Speed and time. 50 rpm and 15 minutes.
Determine by liquid chromatography (2.4.14).
Test solution. Use the filtrate, dilute if necessary with the dissolution medium.
Reference solution. Dissolve a quantity of ropinirole hydrochloride RS in dissolution medium and dilute with dissolution medium to obtain a solution having a known concentration similar to the expected concentration of test solution.
Chromatographic system
– a stainless steel column 7 cm × 3.0 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 1 volume of acetonitrile, 4 volumes of medium,
– flow rate: 0.6 ml per minute,
– spectrophotometer set at 250 nm,
– injection volume: 50 µl.
Inject the reference solution and the test solution.
1 mg of C16H24N2O.HCl is equivalent to 0.8771 mg of C16H24N2O.
- Not less than 85 per cent of the stated amount ofC16H24N2O.
Related substances. Determine by liquid chromatography (2.4.14).
Solvent mixture. A mixture of 80 volumes of a buffer solution prepared by dissolving 5 g of sodium lauryl sulphate in 800 ml of water, adjusted to pH 6.8 with orthophosphoric acid and 20 volumes of methanol.
Test solution. Weigh and powder 20 tablets. Weigh a quantity of the powdered tablets containing about 5.0 mg of ropinirole hydrochloride to a 50-ml volumetric flask, add about 35 ml of the solvent mixture, shake for 30 minutes and mix with the aid of ultrasound and dilute to volume with the solvent mixture and filter.
Reference solution (a). A 0.00002 per cent w/v solution of ropinirol hydrochloride RS in solvent mixture.
Reference solution (b). A 0.00003 per cent w/v solution of ropinirol hydrochloride RS and 0.00005 per cent w/v of ropinirole impurity B RS in solvent mixture.
Chromatographic system
– a stainless steel column 25 cm × 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– column temperature: 50º,
– mobile phase A. a mixture of and 20 volumes of methanol 80 volumes of a buffer solution prepared by dissolving 1.8 g of dibasic potassium phosphate in 1000 ml of water, adjusted to pH 7.4 with orthophosphoric acid,;
- B. a mixture of 80 volumes ofmethanoland 20 volumes of a buffer solution prepared by dissolving 8 g of dibasic potassium phosphate in 1000 ml of water, adjusted to pH 7.4 with orthophosphoric acid,
– a gradient programme using the conditions given below,
– flow rate: 1.0 ml per minute,
– spectrophotometer set at 250 nm,
– injection volume: 100 µl.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
0 85 15
8 85 15
30 30 70
40 10 90
60 10 90
60.1 85 15
70 85 15
Name Relative Correction
retention time factor
Monopropyl ropinirole1 0.24 0.91
Ropinirole N-Oxide2 0.27 1.00
Cyclopentanylindolinone3 0.55 1.00
Hydroxy ropinirole 4 0.64 3.03
Ropinirole impurity B5 0.95 0.71
Ropinirole 1.00 --
Ethyl ropinirole6 1.20 --
Propylidene ropinirole7 1.35 0.62
1 4-[2-(Propylamino)ethyl]indolin-2-one.
2 N-[2-(2-Oxoindolin-4-yl)ethyl]-N-propylpropan-1-amine oxide.
3 1,2a,3,4-Tetrahydro-2H -cyclopenta(cd)indol-2-one.
4 4-[2-(Dipropylamino)ethyl]-1-hydroxy-1,3-dihydro-2H -indol-2-one.
5 4-[2-(Dipropylamino)ethyl]indoline-2,3-dione hydrochloride ;
6 4-[2-(Dipropylamino)ethyl]-1-ethyl-1,3-dihydro-2H -indol-2-one; process impurity included for identification only.
7 (Z)-4-[2-(Dipropylamino)ethyl]-3-propylideneindolin-2-one.
Inject reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to ropinirole hydrochloride and ropinirole impurity B is not less than 2.0, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 5.0 per cent.
Inject reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of each peak due to monopropyl ropinirole and ropinirole impurity B is not more than 0.6 per cent, the area of each peak due to ropinirole N-oxide, cyclopentanylindolinone and hydroxy ropinirole is not more than 0.5 per cent, the area of peak due to propylidene ropinirole is not more than 0.4 per cent, the area of any secondary peak is not more than 0.3 per cent and the sum of area of all the secondary peaks is not more than 2.0 per cent calculated by area normalisation.
Uniformity of content. Determine by liquid chromatography (2.4.14). as described under Assay with the following modification.
Test solution. Disperse 1 tablet in the buffer solution with the aid of ultrasound, and dilute if necessary to obtain a solution containing 0.01 per cent w/v solution of ropinirole.
Inject the test solution and reference solution (a).
Calculate the content of C16H24N2O in the tablets.
Other tests. Comply with the tests stated under Tablets.
Assay. Determine by liquid chromatography (2. 4.14).
Solvent mixture. Dissolve 3.85 g of ammonium acetate in 1000 ml of water, adjusted to pH 2.5 with orthophosphoric acid.
Test solution. Weigh and powder 20 tablets. Weigh a quantity of the powdered tablets containing about 5 mg of Ropinirole Hydrochloride to a 50-ml volumetric flask, add about 25 ml of the solvent mixture, shake for 30 minutes and mix with the aid of ultrasound and dilute to volume with the solvent mixture and filter.
Reference solution (a). A 0.01 per cent w/v solution of ropinirol hydrochloride RS in solvent mixture.
Reference solution (b). A 0.01 per cent w/v solution of ropinirol hydrochloride RS and 0.00005 per cent w/v of ropinirole impurity B RS in solvent mixture.
Chromatographic system
– a stainless steel column 25 cm × 4.6 mm, packed with octylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 14 volumes of acetonitrile, 6 volumes of methanol and 80 volumes of a solution prepared by dissolving 3.85 g of ammonium acetate in 900 ml of water, adjusted to pH 2.5 with orthophosphoric acid and diluting to 1000 ml with water,
– flow rate: 1 ml per minute,
– spectrophotometer set at 250 nm,
– injection volume: 20 µl.
Inject reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to ropinirole hydrochloride and ropinirole impurity B is not less than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 per cent.
Inject reference solution (a) and the test solution.
Calculate the content of C16H24N2O in the tablets.
1 mg of C16H24N2O.HCl is equivalent to 0.8771 mg of C16H24N2O.
Storage. Store protected from moisture, at a temperature below 300.
Labelling. The label states the strength in terms of the equivalent amount of ropinirole.