Ondansetron Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Ondansetron Tablets contain Ondansetron Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of ondansetron (C₁₈H₁₉N₃O).

2 IDENTIFICATION

 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample: Transfer a portion of the powder from ￾nely powdered Tablets, equivalent to 100 mg of ondansetron hydrochloride, to a suitable conical ￾ask. Add 50 mL of alcohol, and swirl. Pass the liquid through a PTFE ￾lter of 0.45-µm pore size into a 50-mL beaker. Evaporate the solvent on a rotary evaporator. Dry the precipitate in an air oven for 1 h at 105°. Prepare a suitable dispersion of the residue in potassium bromide, and record the spectra of the Sample and the standard specimen in the spectral range 3800–650 cm⁻¹.

[Note—It is recommended that a solution of USP Ondansetron Hydrochloride RS in alcohol be prepared at a concentration of 2 mg/mL before the evaporation, followed by the drying steps.]

Acceptance criteria: The Sample shows strong bands at 1621, 1481, 1281, and 758 cm⁻¹, similar to the potassium bromide dispersion of USP Ondansetron Hydrochloride RS.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 2.7 g/L of monobasic potassium phosphate. Adjust with 1 N sodium hydroxide to a pH of 5.4.

Mobile phase: Acetonitrile and Buffer (1:4)

Diluent: Acetonitrile and Buffer (1:1)

Standard solution: 0.05 mg/mL of ondansetron (free base) in Diluent from USP Ondansetron Hydrochloride RS

Sample stock solution: Weigh and ￾nely powder NLT 20 Tablets. Transfer a portion of the powder, equivalent to 50 mg of ondansetron, based on the label claim, to a 100-mL volumetric ￾ask. Add 70 mL of Diluent, and sonicate for about 20 min. Dilute with Diluent to volume. Centrifuge a portion of the solution.

Sample solution: Quantitatively dilute the supernatant with Diluent to obtain a solution having a nominal concentration of 0.05 mg/mL of ondansetron, based on the label claim. Pass through a suitable nylon ￾lter of 0.45-µm pore size, and use the ￾ltrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm

Column: 4.6-mm × 25-cm; 5-µm packing L10

Flow rate: 1.5 mL/min

Injection size: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the label claim of ondansetron (C₁₈H₁₉N₃O) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of ondansetron (free base) in the Standard solution (mg/mL)

Cᵤ = nominal concentration of ondansetron in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: Water; 500 mL, deaerated

Apparatus 2: 50 rpm

Time: 15 min

Standard solution: USP Ondansetron Hydrochloride RS in Medium in a concentration similar to the one expected in the Sample solution

Sample solution: Pass a portion of the solution under test through a suitable ￾lter of 0.45-µm pore size, and dilute, if necessary, with Medium.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 310 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ondansetron (C₁₈H₁₉N₃O) dissolved:

Result = (Aᵤ / Aₛ) × (C / L) × (M / Mₕ) × V × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

C = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

M = molecular weight of ondansetron, 293.36

Mₕ = molecular weight of ondansetron hydrochloride (anhydrous), 329.83

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of C₁₈H₁₉N₃O is dissolved.

Test 2

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium, Apparatus 2, Standard solution, Sample solution, Instrumental conditions, and Analysis: Proceed as directed for Test 1.

Time: 30 min

Tolerances: NLT 80% (Q) of the labeled amount of C₁₈H₁₉N₃O is dissolved.

Test 3

Medium: 0.01 N hydrochloric acid; 500 mL, deaerated

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: Known concentration of USP Ondansetron Hydrochloride RS in Medium, close to the expected concentration of the Sample solution

Sample solution: Pass a portion of the solution under test through a suitable ￾lter of 0.45-µm pore size, and dilute, if necessary, with Medium.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 248 nm

Blank: Medium

Analysis: Same calculation formula as Test 1

Tolerances: NLT 80% (Q) of the labeled amount of C₁₈H₁₉N₃O is dissolved.

Test 4

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard stock solution: 450 µg/mL of USP Ondansetron Hydrochloride RS in Medium

Standard solution: Dilute the Standard stock solution quantitatively and stepwise, if necessary, with Medium to obtain a ￾nal concentration of about (L/500) mg/mL, where L is the Tablet label claim, in mg.

Sample solution: Pass a portion of the solution under test through a suitable ￾lter of 0.45-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 249 nm

Cell path:

– 1 cm for Tablets labeled to contain 4 or 8 mg

– 0.2 cm for Tablets labeled to contain 16 or 24 mg

Blank: Medium

Analysis: Same calculation formula as Test 1

Tolerances: NLT 80% (Q) of the labeled amount of ondansetron is dissolved.

Test 5

Medium, Apparatus 2, Standard solution, Sample solution, Instrumental conditions, and Analysis: Proceed as directed for Test 1.

Time: 30 min

Tolerances: NLT 70% (Q) of the labeled amount of ondansetron is dissolved.

Test 6

Medium: Water; 500 mL, deaerated

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 3.12 g/L of monobasic sodium phosphate dihydrate. Adjust with 1 N sodium hydroxide to a pH of 5.4.

Mobile phase: Acetonitrile and Buffer (40:60)

Standard solution

– For Tablets labeled to contain 4 or 24 mg: 0.01 mg/mL of USP Ondansetron Hydrochloride RS in Medium

– For Tablets labeled to contain 8 mg: 0.02 mg/mL of USP Ondansetron Hydrochloride RS in Medium

Sample solution

– For Tablets labeled to contain 4 or 8 mg: Pass a portion of the solution under test through a suitable ￾lter of 0.45-µm pore size.

– For Tablets labeled to contain 24 mg: Pass a portion of the solution under test through a suitable ￾lter of 0.45-µm pore size. Further dilute 4.0 mL of this solution with Medium to 25.0 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm

Column: 4.6-mm × 15-cm; 5-µm packing L10

Flow rate: 2.0 mL/min

Injection size: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis:

Result = (rᵤ / rₛ) × (C / L) × (M / Mₕ) × V × D × 100

Tolerances: NLT 75% (Q) of the labeled amount of ondansetron is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

Buffer and Mobile phase: Proceed as directed in the Assay.

System suitability solution:

0.05 and 0.1 mg/mL of USP Ondansetron Related Compound A RS and USP Ondansetron Hydrochloride RS, respectively, in Mobile phase

Standard stock solution: Use the Standard solution in the Assay.

Standard solution: 1.5 µg/mL of ondansetron in Mobile phase from the Standard stock solution

Sample solution: Weigh and crush NLT 20 Tablets. Transfer a quantity of powder, equivalent to 50 mg of ondansetron, to a 100-mL volumetric ￾ask. Add about 70 mL of Mobile phase, and sonicate for about 20 min. Dilute with Mobile phase to volume. Centrifuge the solution. Pass a portion of the solution through a suitable nylon ￾lter of 0.45-µm pore size, and use the ￾ltrate.

Chromatographic system: Proceed as directed in the Assay.

Run time: At least 45 min for the Sample solution

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between ondansetron related compound A and ondansetron

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Calculate the percentage of each impurity:

Result = (rᵢ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

Acceptance criteria: See Table 1.

ᵃ Not to be included in total impurities.

▲b 9-Methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one.▲ (ERR 1-Apr-2022)

▲c 9-Methyl-3-methylene-1,2,3,9-tetrahydro-4H-carbazol-4-one.▲ (ERR 1-Apr-2022)

▲d 3-[(Dimethylamino)methyl]-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one.▲ (ERR 1-Apr-2022)

▲e 3-[(1H-Imidazol-1-yl)methyl]-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one.▲ (ERR 1-Apr-2022)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

Change to read:

USP Reference Standards 〈11〉

USP Ondansetron Hydrochloride RS

USP Ondansetron Related Compound A RS

▲3-[(Dimethylamino)methyl]-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one hydrochloride.▲ (ERR 1-Apr-2022)