Action and use
Serotonin 5HT3 antagonist; treatment of nausea and vomiting.
DEFINITION
Ondansetron Injection is a sterile solution of Ondansetron Hydrochloride Dihydrate in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of ondansetron, C18H19N3O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a volume of the injection containing the equivalent of 40 mg of ondansetron add 3 mL of 10M sodium hydroxide, shake and filter. Wash the precipitate with water and dry at 60° at a pressure of 2 kPa. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of ondansetron (RS 418).
TESTS
Acidity
pH, 3.3 to 4.0, Appendix V L.
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) Dilute the injection, if necessary, to give a solution containing the equivalent of 0.2% w/v of ondansetron.
(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 solution of ondansetron for TLC system suitability BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use silica gel F254 as the coating.
(b) Use the mobile phase described below.
(c) Apply 100 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 three 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 obtained with solution (2) (0.4%).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute the injection, if necessary, to give a solution containing the equivalent of 0.1% w/v of ondansetron.
(2) Dilute 1 volume of solution (1) to 50 volumes and further dilute 1 volume of the resulting solution to 10 volumes.
(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.
(5) 0.005% w/v of ondansetron impurity A EPCRS and 0.005% w/v of ondansetron impurity G EPCRS.
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 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 factor between the peaks due to impurity C and 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 may invert.
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 (the first eluting peak in solution (4)) 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 the 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
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute the injection to give a solution containing the equivalent of 0.01% w/v of ondansetron.
(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 (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 injection 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.
