Ondansetron Injection

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 Injection is a sterile solution of Ondansetron Hydrochloride in Water for Injection or of Ondansetron in Water for Injection prepared with the aid of Hydrochloric Acid. It may contain suitable buffers and/or tonicity adjusting agents. It contains an amount of Ondansetron Hydrochloride equivalent to NLT 95.0% and NMT 105.0% 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.

Add the following:

▲B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-May-2024)

3 ASSAY

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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.

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 Hydrochloride RS in Diluent

Sample solution: Nominally 0.1 mg/mL of ondansetron from Injection in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm. For Identification B, use a diode array detector in the range of 200–400 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 1.0% ▲ (USP 1-May-2024)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ondansetron (C₁₈H₁₉N₃O) in the portion of Injection taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (M₁ / M₂) × 100

rᵤ = peak response of ondansetron from the Sample solution

rₛ = peak response of ondansetron from the Standard solution

Cₛ = concentration ▲ (USP 1-May-2024) of USP Ondansetron Hydrochloride RS in the Standard solution (mg/mL)

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

M₁ = molecular weight of ondansetron, ▲293.37▲ (USP 1-May-2024)

M₂ = molecular weight of anhydrous ondansetron hydrochloride, 329.83

Acceptance criteria: 95.0%–105.0%

4 IMPURITIES

Delete the following:

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

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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 Hydrochloride RS and 0.002 mg/mL of USP Ondansetron Related Compound G in Diluent

Standard solution: 0.002 mg/mL each of USP Ondansetron Hydrochloride RS and USP Ondansetron Related Compound D RS in Diluent

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

Sample solution: Nominally 1.0 mg/mL of ondansetron from Injection 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 hydrochloride.

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

Suitability requirements

Resolution: NLT 2.0 between ondansetron and ondansetron related compound G, System suitability solution

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

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

Analysis

Samples: Standard solution and Sample solution

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

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of ondansetron related compound D from the Sample solution

rₛ = peak response of ondansetron related compound D from the Standard solution

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

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

Calculate the percentage of any other specified or unspecified degradation product in the portion of Injection taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1/F) × (M₁ / M₂) × 100

rᵤ = peak response of any other specified or any unspecified degradation product from the Sample solution

rₛ = peak response of ondansetron from the Standard solution

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

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

F = relative response factor (see Table 3)

M₁ = molecular weight of ondansetron, 293.37

M₂ = molecular weight of anhydrous ondansetron hydrochloride, 329.83

Acceptance criteria: See Table 3. The reporting threshold is 0.1%.

5 SPECIFIC TESTS

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Bacterial Endotoxins Test 〈85〉: ▲Meets the requirements▲ (USP 1-May-2024)

Add the following:

▲• Sterility Tests 〈71〉: Meets the requirements▲ (USP 1-May-2024)

pH 〈791〉: 3.3–4.0

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

Other Requirements: It meets the requirements under Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or in multiple-dose containers, preferably of Type I glass, at a temperature between 2° and 30°, protected from light.

Change to read:

USP Reference Standards 〈11〉

USP Ondansetron Hydrochloride RS

▲ (USP 1-May-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-Imidazole-1-yl)methyl]-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one.

C₁₇H₁₇N₃O 279.34▲ (USP 1-May-2024)