Lacosamide 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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1 DEFINITION

Lacosamide Oral Solution contains NLT 90.0% and NMT 105.0% of the labeled amount of lacosamide (C₁₃H₁₈N₂O₃).

2 IDENTIFICATION

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

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

Procedure

Solution A: To each liter of water add 0.5 mL of trifluoroacetic acid.

Solution B: To each liter of acetonitrile add 0.5 mL of trifluoroacetic acid.

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (25:75)

Standard solution: 1.0 mg/mL of USP Lacosamide RS in Diluent

Sample solution: Nominally 1.0 mg/mL of lacosamide from Oral Solution prepared as follows. Transfer a volume of Oral Solution to a suitable volumetric flask. Dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm. For Identification A, use a diode array detector in the range of 230–300 nm.

Column: 4.6-mm × 25-cm; 5-μm packing L1

Temperatures:

Autosampler: 10°

Column: 30°

Flow rate: 1.5 mL/min

Injection volume: 4 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lacosamide (C₁₃H₁₈N₂O₃) in the portion of Oral Solution taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Lacosamide RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–105.0%

4 PERFORMANCE TESTS

Deliverable Volume 〈698〉: Meets the requirements

5 IMPURITIES

Organic Impurities

Solution A: Acetonitrile and water (10:90). To each liter add 0.56 mL of trifluoroacetic acid.

Solution B: To each liter of acetonitrile add 0.5 mL of trifluoroacetic acid.

Mobile phase: See Table 2.

Table 2

Diluent: Acetonitrile and water (25:75)

System suitability solution: 1 mg/mL of USP Lacosamide RS and 0.002 mg/mL each of USP Lacosamide Related Compound D RS and USP

Lacosamide Related Compound F RS in Diluent

Sensitivity solution: 0.001 mg/mL of USP Lacosamide RS in Diluent

Standard solution: 0.002 mg/mL of USP Lacosamide RS in Diluent

Sample solution: Prepare as directed in the Assay.

Chromatographic system: Proceed as directed in the Assay, except for the Injection volume.

Injection volume: 5 μL

System suitability

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

[Note—The relative retention times for lacosamide related compound D, lacosamide related compound F, and lacosamide are 0.36, 0.48, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between lacosamide related compound D and lacosamide related compound F, System suitability solution 

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Oral Solution taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of lacosamide from the Standard solution

C_S = concentration of USP Lacosamide RS in the Standard solution (mg/mL)

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

Acceptance criteria: The reporting threshold is 0.1%.

Lacosamide related compound D: NMT 0.80%

Any individual unspecified degradation product: NMT 0.20%

Total degradation products: NMT 2.0%

6 SPECIFIC TESTS

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 requirements of the test for absence of Escherichia coli.

pH 〈791〉: 3.8–5.0

7 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Lacosamide RS

USP Lacosamide Related Compound D RS

2-Amino-N-benzyl-3-methoxypropanamide oxalate.

C₁₁H₁₆N₂O₂ · C₂H₂O₄ 298.30

USP Lacosamide Related Compound F RS

2-Acetamido-N-benzyl-3-hydroxypropanamide.

C₁₂H₁₆N₂O₃ 236.27 (USP 1-May-2021)