Levetiracetam Oral Solution

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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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click https://www.uspnf.com/rb-levetiracetam-oral-solution-20191122.

1 DEFINITION

Levetiracetam Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of levetiracetam (C₈H₁₄N₂O₂ ).

2 IDENTIFICATION

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

3 ASSAY

Procedure

Solution A: Dilute 1 mL of phosphoric acid with water to 1 L.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 1.0 mg/mL of USP Levetiracetam RS in Solution A

Sample solution: Nominally 1.0 mg/mL of levetiracetam prepared as follows. Transfer a suitable volume of the Oral Solution to a suitable volumetric flask to obtain 1.0 mg/mL final concentration of levetiracetam. Add 60% of the flask volume of Solution A, and sonicate at room temperature for 5 min with intermittent shaking. Allow the solution to cool, and dilute with Solution A to volume. Pass a portion of the solution under test through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 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 labeled amount of levetiracetam (C₈H₁₄N₂O₂ ) in the portion of Oral Solution 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 (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Organic Impurities

Solution A: Dilute 2 mL of phosphoric acid with water to 1 L.

Solution B: Acetonitrile

Diluent: Acetonitrile and Solution A (5:95)

Mobile phase: See Table 2.

Table 2

System suitability solution: 0.2 mg/mL of USP Levetiracetam RS and 0.1 mg/mL of USP Levetiracetam Related Compound A RS in Diluent prepared 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, and then neutralize by adding 0.1 N hydrochloric acid at 10% of the flask volume.

Add the required amount of USP Levetiracetam Related Compound A RS, sonicate to dissolve, and dilute with Diluent to volume. [Note—This solution contains levetiracetam, levetiracetam acid, and levetiracetam related compound A.]

Standard solution: 3 μg/mL of USP Levetiracetam RS in Solution A

Sample solution: Nominally 2 mg/mL of levetiracetam prepared as follows. Transfer a suitable volume of the Oral Solution to a suitable volumetric flask. Add 60% of the flask volume of Solution A, and sonicate at room temperature for 5 min with intermittent shaking. Allow the solution to cool, and dilute with Solution A to volume. Pass a portion of the solution through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between levetiracetam related compound A and levetiracetam acid, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oral Solution taken:

Result = (r_U/r_S)x(C_S/C_U) × (1/F) × 100

r_U = peak response of the impurity 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 (mg/mL)

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

F = relative response factor for each impurity (see Table 3)

Acceptance criteria: See Table 3.

Table 3

^a (S)-N-(1-Amino-1-oxobutan-2-yl)-4-chlorobutanamide.

^b This is a process impurity and included for peak identification purposes only.

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

5 SPECIFIC TESTS

Change to read:

pH 〈791〉: 4.8–7.0 (RB 1-Dec-2019)

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 10² cfu/mL.

The total yeasts and molds count does not exceed 10¹ cfu/mL. It meets the requirement of the test for absence of Escherichia coli.

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Levetiracetam RS

USP Levetiracetam Related Compound A RS

(S)-N-(1-Amino-1-oxobutan-2-yl)-4-chlorobutanamide.

C₈H₁₅ClN₂O₂ 206.67