Ondansetron

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 contains NLT 98.0% and NMT 102.0% of ondansetron (C₁₈H₁₉N₃O), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: ▲197A or▲ (USP 1-Aug-2024) 197K

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

Change to read:

Procedure

▲Solution A:** 2.4 g/L of monobasic sodium phosphate, anhydrous and 0.6 g/L of sodium 1-heptanesulfonate in water. Adjust with 0.5 N sodium hydroxide to a pH of 5.4.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (30:70). To each liter of this solution add 1 mL of formic acid.

Standard solution: 0.1 mg/mL of USP Ondansetron RS in Diluent

Sample solution: 0.1 mg/mL of Ondansetron in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm

Column: 4.6-mm × 25-cm; 5-μm packing L11

Temperatures

Autosampler: 15°

Column: 40°

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%▲ (USP 1-Aug-2024)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ondansetron (C₁₈H₁₉N₃O) in the portion of Ondansetron taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of ondansetron from the Sample solution

rₛ = peak response of ondansetron from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

Chloride and Sulfate 〈221〉, Chloride

▲Sample: 1 g

Acceptance criteria: The turbidity produced in the Sample does not exceed that produced in 0.3 mL of 0.020 N hydrochloric acid (NMT 0.02%).▲ (USP 1-Aug-2024)

Delete the following:

▲• Limit of Ondansetron Related Compound D▲ (USP 1-Aug-2024)

Change to read:

Organic Impurities

▲Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system:** Proceed as directed in the Assay.

System suitability solution: 1 mg/mL of USP Ondansetron RS and 0.001 mg/mL of USP Ondansetron Related Compound G in Diluent

Standard solution: 0.001 mg/mL each of USP Ondansetron RS and USP Ondansetron Related Compound D RS in Diluent

Sensitivity solution: 0.5 μg/mL each of USP Ondansetron RS and USP Ondansetron Related Compound D RS from the Standard solution in Diluent

Sample solution: 1.0 mg/mL of Ondansetron in Diluent

System suitability

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

[Note—The relative retention times in Table 2 are provided as information that could aid in peak assignment.]

ᵃ 1H-Imidazole.

ᵇ 2-Methyl-1H-imidazole.

ᶜ 3-[(Dimethylamino)methyl]-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one.

ᵈ 9-Methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one.

ᵉ Disregard the peak corresponding to methylene bisondansetron. Quantified in the test for Limit of Methylene Bisondansetron.

Suitability requirements

Resolution: NLT 2.0 between ondansetron and ondansetron related compound G

Relative standard deviation: NMT 5.0% for ondansetron, Standard solution

Signal-to-noise ratio: NLT 10 for ondansetron, Sensitivity solution

Analysis

Calculate the percentage of ondansetron related compound D in the portion of Ondansetron taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

Calculate the percentage of any unspecified impurity in the portion of Ondansetron taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

Acceptance criteria: See Table 3.

The reporting threshold is 0.05%.

Table 3

▲ (USP 1-Aug-2024)

Add the following:

▲• Limit of Methylene Bisondansetron (If Present)

Buffer: 2.4 g/L of monobasic sodium phosphate, anhydrous in water. Adjust with 0.5 N sodium hydroxide to a pH of 6.5.

Mobile phase: Acetonitrile and Buffer (65:35)

Peak identification solution: 1 mg/mL of USP Ondansetron Resolution Mixture RS in Mobile phase

Standard solution: 0.002 mg/mL of USP Ondansetron RS in Mobile phase

Sensitivity solution: 0.001 mg/mL of USP Ondansetron RS from the Standard solution in Mobile phase

Sample solution: 1.0 mg/mL of Ondansetron in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm

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

Temperatures

Autosampler: 15°

Column: 35°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 5 times the retention time of ondansetron

System suitability

Samples: Standard solution and Sensitivity solution

[Note—The relative retention times for ondansetron and methylene bisondansetron are 1.0 and 3.7, respectively.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 5.0%

Signal-to-noise ratio: NLT 10

Analysis

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

F = relative response factor, 0.63

Acceptance criteria: NMT 0.4%▲ (USP 1-Aug-2024)

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I, Method Ia: NMT 3.0%

Add the following:

▲Bacterial Endotoxins Test 〈85〉: Where the label states that Ondansetron must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxins is such that the requirement under the relevant dosage form monograph(s) in which Ondansetron is used can be met.▲ (USP 1-Aug-2024)

Add the following:

▲Microbial Enumeration Tests 〈61〉: The total aerobic microbial count does not exceed 10² cfu/g and the total combined molds and yeast count does not exceed 50 cfu/g.▲ (USP 1-Aug-2024)

6 ADDITIONAL REQUIREMENTS

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

Add the following:

▲Labeling: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.▲ (USP 1-Aug-2024)

Change to read:

USP Reference Standards 〈11〉

USP Ondansetron RS ▲▲ (USP 1-Aug-2024)

USP Ondansetron Related Compound D RS

9-Methyl-3-methylene-1,2,3,9-tetrahydro-4H-carbazol-4-one.

▲C₁₄H₁₃NO 211.26

USP Ondansetron Related Compound G

3-[(1H-Imidazol-1-yl)methyl]-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one.

C₁₇H₁₇N₃O 279.34

USP Ondansetron Resolution Mixture RS

Contains a mixture of the following 3 compounds:

Ondansetron hydrochloride.

Ondansetron related compound A;

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

C₁₈H₂₂N₂O · HCl 292.81

Methylene bisondansetron;

6,6'-Methylenebis{9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-1,2,3,9-tetrahydro-4H-carbazol-4-one}.

C₃₆H₃₈N₆O₂ 598.75▲ (USP 1-Aug-2024)