Levetiracetam 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

Levetiracetam Injection is a sterile solution of levetiracetam in Water for Injection and contains NLT 90.0% and NMT 110.0% of the labeled amount of levetiracetam (C₈H₁₄N₂O₂ ). Levetiracetam Injection may contain buffering and isotonicity agents. Levetiracetam Injection contains no antimicrobial agent.

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.

3 ASSAY

Procedure

Buffer: 1.0 g/L of anhydrous dibasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 6.0.

Mobile phase: Acetonitrile and Buffer (6:94)

Diluent: Acetonitrile and water (6:94)

System suitability solution: Solution containing levetiracetam and levetiracetam acid prepared from a solution of 0.2 mg/mL of USP

Levetiracetam RS as follows. Dissolve the required amount of USP Levetiracetam RS in 10% of the final volume of 0.1 N potassium hydroxide. Let the mixture react at room temperature for about 15 min, then neutralize by adding 10% of the flask volume of 0.1 N hydrochloric acid. Dilute with Diluent to volume.

Standard solution: 100 μg/mL of USP Levetiracetam RS in Diluent. Sonication may be used to aid in dissolution if necessary.

Sample solution: Nominally 100 μg/mL of levetiracetam from NLT 2 mL of Injection in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 205 nm

Column: 3.9-mm × 30-cm; 10-μm packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of levetiracetam

System suitability

Samples: System suitability solution and Standard solution

[Note—Identify the peaks using the relative retention times given in Table 1.]

Suitability requirements

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

Relative standard deviation: NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of levetiracetam (C₈H₁₄N₂O₂ ) in the portion of Injection taken:

Result = (r_U/r_S)x(C_S/C_U ) × 100

r_U = peak response of levetiracetam from the Sample solution

r_S = peak response of levetiracetam from the Standard solution

C_S = concentration of USP Levetiracetam RS in the Standard solution (μg/mL)

C_U = nominal concentration of levetiracetam in the Sample solution (μg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

4.1 Organic Impurities

Buffer, Mobile phase, Diluent, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.1 μg/mL of USP Levetiracetam RS in Diluent

4.2 System suitability

Samples: System suitability solution and Standard solution

[Note—Identify the peaks using the relative retention times in Table 1.]

4.3 Suitability requirements

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

Relative standard deviation: NMT 10.0%, Standard solution

Signal-to-noise ratio: NLT 10, Standard solution

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of levetiracetam acid and any other unspecified degradation product in the portion of Injection taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of levetiracetam acid or any individual unspecified degradation product from the Sample solution

r_S = peak response of levetiracetam from the Standard solution

C_S = concentration of USP Levetiracetam RS in the Standard solution (μg/mL)

C_U = nominal concentration of levetiracetam in the Sample solution (μg/mL)

Acceptance criteria: See Table 1.

Table 1

^a (S)-2-(2-Oxopyrrolidin-1-yl)butanoic acid.

5 SPECIFIC TESTS

pH 〈791〉: 5.0–6.0

Bacterial Endotoxins Test 〈85〉: Contains NMT 0.175 USP Endotoxin Units/mg of levetiracetam

Sterility Tests 〈71〉: Meets the requirements when tested as directed for Aqueous Solutions under Test for Sterility of the Product to Be

Examined, Membrane Filtration

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed Type I glass vials. Store at controlled room temperature.

Labeling: Label the article to indicate that the Injection is to be diluted prior to administration.

USP Reference Standards 〈11〉

USP Levetiracetam RS