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

2 IDENTIFICATION

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

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

[Note—Alternatively, the UV spectra of the major peaks of the Sample solution and the Standard solution, as obtained in the Assay, may be used to meet the Acceptance criteria.]

Diluent: 0.1 N hydrochloric acid

Standard solution: 8 µg/mL of USP Ondansetron RS in Diluent

Sample solution: Nominally 8 µg/mL of ondansetron from Tablets in Diluent. Pass a portion of the solution through a suitable ￾lter of 0.45-µm pore size, discarding the ￾rst few milliliters of the ￾ltrate.

Wavelength range: 200–400 nm

Cell: 1 cm

Blank: Diluent

Acceptance criteria: The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution.

3 ASSAY

Procedure

Diluent: 0.01 N hydrochloric acid

Buffer: 2.72 g/L of monobasic potassium phosphate in water. Adjust with 1 N sodium hydroxide or 0.5 N sodium hydroxide to a pH of 5.4.

Mobile phase: Acetonitrile and Buffer (48:52)

System suitability solution: 0.02 mg/mL of USP Ondansetron Related Compound A RS and 0.006 mg/mL of USP Ondansetron RS in Diluent

Standard solution: 40 µg/mL of USP Ondansetron RS in Diluent

Sample stock solution: Nominally equivalent to 400 µg/mL of ondansetron prepared as follows. Transfer 10 Tablets to a suitable volumetric ￾ask. Add Diluent to ￾ll about 60% of the ￾ask volume. Shake by mechanical means for about 5 min, and dilute with Diluent to volume. Pass a portion of this solution through a polypropylene membrane of 0.45-µm pore size, discarding the ￾rst 5 mL of the ￾ltrate.

Sample solution: Nominally 40 µg/mL of ondansetron in Diluent, from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm. If the procedure is used for Identi￾cation B, use a diode array detector set at 200–400 nm.

Column: 4.6-mm × 25-cm; packing L10

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for ondansetron and ondansetron related compound A are 1.0 and 1.1, respectively.]

Suitability requirements:

Resolution: NLT 1.5 between ondansetron related compound A and ondansetron, System suitability solution

Tailing factor: NMT 2.0 for the ondansetron peak, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount 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 USP Ondansetron RS 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

Disintegration 〈701〉

Test 1

Time: NMT 10 s

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

Time: NMT 60 s

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 500 mL, deaerated

Apparatus 2: 50 rpm

Time: 10 min

Detector: UV 310 nm

Cell:

For 4- and 8-mg Tablets: 1 cm

For 16-mg Tablets: 0.5 cm

For 24-mg Tablets: 0.2 cm

Standard solution: (L/500) mg/mL of USP Ondansetron RS in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable ￾lter.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ondansetron (C₁₈H₁₉N₃O) dissolved:

Result = (Aᵤ / Aₛ) × (Cₛ / L) × V × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

Cₛ = concentration of USP Ondansetron RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

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

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Buffer: Prepare as directed in the Assay.

Mobile phase: Acetonitrile and Buffer (1:4)

System suitability solution: 2 µg/mL each of USP Ondansetron Related Compound D RS, 2-methylimidazole, and USP Ondansetron RS in Mobile phase.

[Note—First dissolve in acetonitrile, and then dilute with Mobile phase to volume.]

Standard solution: 2 µg/mL of USP Ondansetron RS in Mobile phase

Sensitivity solution: 0.2 µg/mL of USP Ondansetron RS, from the Standard solution in Mobile phase

Sample solution: Nominally equivalent to 400 µg/mL of ondansetron prepared as follows. Transfer 10 Tablets to a suitable volumetric ￾ask. Add Mobile phase to ￾ll about 60% of the ￾ask volume. Shake by mechanical means for about 5 min, and dilute with Mobile phase to volume. Centrifuge a portion of this solution at 3000 rpm for 10 min. Use the supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm

Column: 4.6-mm × 25-cm; packing L10

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: About 60 min

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements:

Resolution: NLT 1.5 between ondansetron and any adjacent peak, System suitability solution

Column e￾ciency: NLT 8000 theoretical plates for ondansetron, System suitability solution

Tailing factor: NMT 2.0 for the ondansetron peak, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 15, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Tablets taken:

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

rᵢ = peak area of each individual impurity from the Sample solution

rₛ = peak area of ondansetron from the Standard solution

Cₛ = concentration of USP Ondansetron RS in the Standard solution (µg/mL)

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

F = relative response factor for each impurity (see Table 1)

Acceptance criteria: See Table 1.

Table 1

6 ADDITIONAL REQUIREMENTS

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

Labeling: The labeling states the Disintegration test used only if Test 1 is not used.

Change to read:

USP Reference Standards 〈11〉

USP Ondansetron RS

USP Ondansetron Related Compound A RS

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

C₁₈H₂₃N₂O · HCl ▲292.81▲ (ERR 1-Feb-2022)

USP Ondansetron Related Compound D RS

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

C₁₄H₁₃NO 211.26