QuetiapineFumarate Prolonged-release Tablets
Quetiapine Sustained-release Tablets; Quetiapine Extended-release Tablets
Quetiapine Fumarate Prolonged-release Tablets manufactured by different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable,as the dissolution profile of the products of different manufactures may not be the same.
Quetiapine Fumarate Prolonged-release Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of quetiapine, C21H25N3,O2S.
Usual strengths.200 mg; 300 mg; 400 mg.
Identification
- Shake a quantity of the powdered tablets containing about 10 mg of Quetiapine Fumarate add 10 ml ofacetone. Sonicate for 10 minutes. Allow the solution to equilibrate to room temperature. Evaporate theacetone completely. Add 2 ml of chloroform. Gently swirl for several minutes and use the filtrate. Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained with quetiapine fumarate RS treated in the same manner or with the reference spectrum of quetiapine fumarate.
- 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 (c).
Tests
Dissolution (2.5.2).Complies with the test stated under Tablets.
Related substances.Determine by liquid chromatography (2.4.14).
Solvent mixture, test solution, reference solution (b) and chromatographic system as described under Assy.
Name Relative Correction
retention time factor
Fumaric acid 0.1 ---
Quetiapine related compound G1 0.48 0.71
Quetiapine related compound H20.57 1.0
Quetiapinedesethoxy30.87 ---
Quetiapine 1.0 ---
Quetiapine related compound B4 1.9 ---
Unknown impurity --- 1.0
1Dibenzo[b,f][1,4]thiazepin-11(10H)-one,
24-(Dibenzo[b,f][1,4]thiazepin-11-yl)-1-[2-(2-hydroxy ethoxy) ethyl] piperazine 1-oxide,
32-[4-(dibenzo[b,f][1,4]thiazepin-11-yl) piperazin-1-yl]ethanol,
411-(piperazin-1-yl) dibenzo [b,f][1,4] thiazepin.
Inject reference solution (b). The test is not valid unless the resolution between quetiapine related compound G and quetiapine related compound H is not less than 1.5;between quetiapinedesthoxy and quetiapine peak is not less than 2.0.
Inject the test solution. In the chromatogram obtained with test solution the area of peak due to quetiapine related compound G, H and any other secondary peaks is not more than 0.2 per cent and the sum of areas of all the secondary peaks is not more than 0.4 per cent.Ignore any peak with an area less than 0.05 per cent, calculated by area normalization.
Other tests. Comply with the tests stated under Tablets.
Assay.Determine by liquid chromatography (2.4.14).
Solvent mixture.Equal volumes of acetonitrile and water.
Test solution. Disperse a quantity of the powdered tablets containing about 250 mg of QuetiapineFumarate to a 500 ml- volumetric flask, add 50 ml of acetonitrile swirl to wet and allow to stand for 10 minutes. Add 160 ml of solvent mixture and extract for about 10 minutes, dilute to 500.0 ml with solvent mixture.Dilute 10.0 ml of this supernatant to 25.0 ml with mobile phase.
Reference solution (a). A 0.005 per cent w/v solution of quetiapine related compound H RS in mobile phase.
Reference solution (b).Weigh accurately 5 mg of quetiapine system suitability RS it contains quetiapine fumarate and about 0.1 per cent each of following impurity quetiapine related compound B, quetiapine related compound G and quetiapinedesethoxyto a 10 ml- volumetric flask. Add 7 ml of mobile phase and sonicate to dissolve. Add 1 ml of reference solution (a) and dilute with mobile phase to volume.
Reference solution (c).A 0.02 per cent w/v solution of quetiapinefumarate RS in mobile phase.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 390 volumes of a buffer solution prepared by dissolving 2.6 g of dibasic ammonium phosphatein 1000 ml of water, 70 volumes of acetonitrileand 540 volumes of methanol,
– flow rate:1.3 ml per minute,
– spectrophotometer set at 230 nm,
– injection volume: 30 µl.
Inject reference solution (b). The test is not valid unless the resolution between quetiapine related compound G and quetiapine related compound H is not less than 1.5 and between quetiapinedesthoxy and quetiapine peak is not less than 2.0.
Inject reference solution (c).The test is not valid unless the tailing factor is not more than 1.5 and the relative standard deviation for replicate injections is not more than 2.0 per cent.
Inject the reference solution (c) and the test solution.
Calculate the content of C21H25N3,O2S in the tablets.
Storage. Store in well-closed containers at controlled room temperature.