Ondansetron
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C18H19N3O 293.36

4H-Carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]- (±)-.
(±)-2,3-Dihydro-9-methyl-3-[(2-methylimidazol-1-yl)methyl]carbazol-4(1H)-one [99614-02-5].
» Ondansetron contains not less than 98.0 percent and not more than 102.0 percent of C18H19N3O, calculated on the anhydrous basis.
Packaging and storage— Preserve in tight, light-resistant containers at room temperature.
Identification—
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Water, Method Ia 921: not more than 3.0%.
Residue on ignition 281: not more than 0.1%.
Chloride 221 To 1 g of the substance under test, add 30 to 40 mL of water, and warm gently, if necessary, until no more dissolves. Mix well, and pass through a filter paper that gives a negative test for chloride. Add I mL of nitric acid and 1 mL of silver nitrate TS. Dilute with water to 50 mL. Mix well, and allow to stand for 5 minutes protected from direct sunlight: any turbidity formed is not greater than that produced in a similarly treated control solution containing 0.3 mL of 0.020 N hydrochloric acid (0.02%).
Limit of ondansetron related compound D—
Phosphate buffer— Dissolve about 2.72 g of monobasic potassium phosphate in 900 mL of water. Adjust with 1 N sodium hydroxide or 0.5 N sodium hydroxide to a pH of 5.4, dilute to 1000 mL, and mix.
Mobile phase— Prepare a filtered and degassed mixture of Phosphate buffer and acetonitrile (80:20). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Dissolve an amount of USP Ondansetron Related Compound D RS in Mobile phase, and dilute stepwise with Mobile phase, to obtain a solution having a known concentration of about 0.4 µg per mL.
Resolution solution— Prepare a solution of USP Ondansetron Related Compound D RS and USP Ondansetron Related Compound C RS in Mobile phase having a known concentration of about 0.6 µg per mL and 1.0 µg per mL, respectively.
Test solution— Transfer about 50 mg of Ondansetron, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 328-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The column temperature is maintained at 30. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for ondansetron related compound C and 1.0 for ondansetron related compound D; and the resolution, R, between ondansetron related compound C and ondansetron related compound D is not less than 1.5. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the column efficiency is not less than 8000 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of ondansetron related compound D in the ondansetron taken by the formula:
10(C/W)(rU / rS)
in which C is the concentration, in µg per mL, of USP Ondansetron Related Compound D RS in the Standard solution; W is the weight, in mg, of ondansetron taken to prepare the Test solution; and rU and rS are the peak responses of ondansetron related compound D obtained from the Test solution and the Standard solution, respectively: not more than 0.10% is found.
Related compounds—
Phosphate buffer, Mobile phase, Resolution solution, Standard preparation, and Chromatographic system— Prepare as directed in the Assay.
Test solution— Use the Assay preparation prepared as directed in the Assay.
Procedure— Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of each impurity in the portion of Ondansetron taken by the formula:
100(ri / rs)
in which ri is the peak area for each impurity; and rs is the sum of the areas of all the peaks: not more than 0.1% of any individual impurity is found; and not more than 0.5% of total impurities is found, including ondansetron related compound D. [note—Disregard the peak corresponding to ondansetron related compound D at a relative retention time of about 0.4.]
Assay—
Phosphate buffer— Dissolve about 2.72 g of monobasic potassium phosphate in 900 mL of water. Adjust with 1 N sodium hydroxide or 0.5 N sodium hydroxide to a pH of 5.4, dilute to 1000 mL, and mix.
Mobile phase— Prepare a filtered and degassed mixture of Phosphate buffer and acetonitrile (52:48). Make adjustments if necessary (see System Suitability under Chromatography 621).
Resolution solution— Prepare a solution of USP Ondansetron RS and USP Ondansetron Related Compound A RS in Mobile phase having a known concentration of about 0.09 mg per mL and 0.05 mg per mL, respectively.
Standard preparation— Dissolve an accurately weighed quantity of USP Ondansetron RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.090 mg per mL.
Assay preparation— Transfer about 45 mg of Ondansetron, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Pipet 5.0 mL of this solution into a 50-mL volumetric flask. Dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 216-nm detector and a 4.6-mm 25-cm column that contains packing L10. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 30. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.1 for ondansetron related compound A and 1.0 for ondansetron; and the resolution, R, between ondansetron related compound A and ondansetron is not less than 1.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the ondansetron peaks. Calculate the quantity, in mg, of C18H19N3O in the portion of Ondansetron taken by the formula:
500C(rU / rS)
in which C is the concentration, in mg per mL, of USP Ondansetron RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Ravi Ravichandran, Ph.D.
Senior Scientist
1-301-816-8330
(MDPP05) Monograph Development-Psychiatrics and Psychoactives
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
USP32–NF27 Page 3137
Pharmacopeial Forum: Volume No. 30(6) Page 2021
Chromatographic Column—
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.