Action and use
Serotonin 5HT3 antagonist; treatment of nausea and vomiting.
DEFINITION
Ondansetron Tablets contain Ondansetron Hydrochloride Dihydrate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of ondansetron, C18H19N3O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing the equivalent of 30 mg of ondansetron with 20 mL of acetonitrile, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ondansetron hydrochloride (RS 419).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 500 mL of water, at a temperature of 37o, as the medium.
PROCEDURE
(1) After 30 minutes, withdraw a sample of the medium, and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 310 nm, Appendix II B, using water in the reference cell.
(2) Measure the absorbance of a 0.001% w/v solution of ondansetron hydrochloride dihydrate BPCRS using water in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of ondansetron, C18H19N3O, in the medium from the absorbances obtained and using the declared content of C18H19N3O in ondansetron hydrochloride dihydrate BPCRS.
LIMITS
The amount of ondansetron released is not less than 75% (Q) of the stated amount.
Impurity B
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in solution A.
Solution A: 0.5 volumes of 13.5M ammonia, 100 volumes of ethanol (96%) and 100 volumes of methanol.
(1) Shake a quantity of the powdered tablets containing the equivalent of 20 mg of ondansetron with 25 mL of acetonitrile, filter and evaporate the filtrate to dryness using a rotary evaporator. Dissolve the residue in 2 mL of solution A.
(2) Dilute 1 volume of solution (1) to 50 volumes and dilute 1 volume of the resulting solution to 5 volumes.
(3) 0.25% w/v of ondansetron for TLC system suitability BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254.
(b) Use the mobile phase as described below.
(c) Apply 10 μL of each solution.
(d) Develop the plate to 15 cm.
(e) Remove the plate, dry in air and examine under ultraviolet light (254 nm).
MOBILE PHASE
1 volume of 13.5M ammonia, 20 volumes of methanol, 25 volumes of ethyl acetate and 45 volumes of dichloromethane.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows 3 clearly separated spots (impurity A, Rf value of about 0.3; impurity B, Rf value of about 0.4; ondansetron, Rf value of about 0.6).
LIMITS
In the chromatogram obtained with solution (1): any secondary spot corresponding to impurity B is not more intense than the spot in the chromatogram obtained with
solution (2) (0.4%).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing the equivalent of 20 mg of ondansetron with 25 mL of acetonitrile, filter and evaporate the filtrate to dryness. Dissolve the residue in 20 mL of mobile phase.
(2) Dilute 1 volume of solution (1) to 50 volumes with the mobile phase and dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.
(3) 0.0004% w/v each of ondansetron impurity E EPCRS and ondansetron impurity F EPCRS.
(4) 0.05% w/v of ondansetron impurity standard BPCRS (containing impurities C and D) in the mobile phase.
(5) 0.005% w/v of ondansetron impurity A EPCRS and 0.005% w/v of ondansetron impurity G EPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with cyanosilyl silica gel for chromatography (5 μm) (Spherisorb CN is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 216 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
20 volumes of acetonitrile R1 and 80 volumes of 0.02M sodium dihydrogen orthophosphate dihydrate, previously adjusted to pH 5.4 with 1M sodium hydroxide.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to impurity C and impurity D is at least 2.5.
LIMITS
Identify any peak corresponding to impurity C (the first eluting peak in solution (4)) and multiply the area of this peak by a correction factor of 0.6.
The peaks due to impurity E and impurity F in solution (3) and the peaks due to impurity A and impurity G in solution (5) may co-elute or be inverted.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity D (the second eluting peak in solution (4)) is not greater than 0.75 times
the area of the principal peak in the chromatogram obtained with solution (2) (0.15%);
the area of any peak corresponding to impurity C is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of the peaks corresponding to impurities E and F is not greater than the area of the corresponding peaks in the chromatogram obtained with solution (3) (0.4%);
the sum of the areas of any peaks corresponding to impurities A and G is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.4%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks apart from any peaks corresponding to impurity C and impurity D is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in solution B.
Solution B: Equal volumes of acetonitrile and mobile phase.
(1) Mix a quantity of the powdered tablets containing the equivalent of 20 mg of ondansetron and 150 mL of solution B for 30 minutes with the aid of ultrasound, shaking every 5 minutes, and allow to cool. Add sufficient solution B to produce 200 mL and filter.
(2) 0.0125% w/v of ondansetron hydrochloride dihydrate BPCRS.
(3) 0.05% w/v of ondansetron impurity standard BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless:
in the chromatogram obtained with solution (1), the symmetry factor for the peak due to ondansetron is less than 3.0;
in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity C and impurity D is at least 2.5.
DETERMINATION OF CONTENT
Calculate the content of C18H19N3O in the tablets using the declared content of C18H19N3O in ondansetron hydrochloride dihydrate BPCRS.
LABELLING
The quantity of active ingredient is stated in terms of the equivalent amount of ondansetron.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Ondansetron Hydrochloride Dihydrate.
