Lacosamide Tablets

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-lacosamide-tabs-20220930.

1 DEFINITION

Lacosamide Tablets 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

Mobile phase: Acetonitrile and water (13:87). To each liter add 0.75 mL of methanesulfonic acid.

Diluent 1: Methanol and water (1.5: 98.5)

Diluent 2: Methanol and water (50:50)

System suitability solution: 1 mg/mL of USP Lacosamide RS and 2.0 μg/mL each of USP Lacosamide Related Compound D RS and USP

Lacosamide Related Compound F RS in Diluent 1

Standard solution: 1 mg/mL of USP Lacosamide RS in Diluent 1

Sample stock solution: Nominally 2 mg/mL of lacosamide from Tablets (NLT 10) prepared as follows. Transfer the Tablets to an appropriate volumetric flask and add a suitable quantity of Diluent 2 to the flask. Shake for 30 min to disperse the Tablets. Dilute with water to volume, sonicate for 10 min, and let settle for 30 min.

Sample solution: Nominally 1 mg/mL of lacosamide from Sample stock solution prepared as follows. Transfer a portion of Sample stock solution to an appropriate volumetric flask and dilute with water to volume to obtain a final composition that is the same as Diluent 1.

Centrifuge the solution and use the supernatant.

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 × 15-cm; 5-μm packing L7

Temperatures

Autosampler: 10°

Column: 35°

Flow rate: 2 mL/min

Injection volume: 5 μL

Run time: NLT 2.5 times the retention time of lacosamide

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for lacosamide related compound D, lacosamide related compound F, and lacosamide are 0.37, 0.47, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between lacosamide related compound D and lacosamide related compound F, System suitability solution

Tailing factor: NMT 2, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lacosamide (C₁₃H₁₈N₂O₃) in the portion of Tablets 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

Change to read:

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid VS; 900 mL

Apparatus 2: 50 rpm with suitable sinker , if necessary (RB 1-Oct-2022)

Time: 30 min

Mobile phase: Acetonitrile and water (30:70). To each liter add 1 mL of trifluoroacetic acid.

Standard solution: (L/900) mg/mL of USP Lacosamide RS in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of suitable pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 5-cm; 3-μm packing L1

Temperatures

Autosampler: 10°

Column: 35°

Flow rate: 1 mL/min

Injection volume: 2 μL

Run time: NLT 2.5 times the retention time of lacosamide

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of lacosamide (C₁₃H₁₈N₂O₃) dissolved:

Result = (r /r ) × C × V × (1/L) × 100

r = peak response from the Sample solution

r = peak response from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of lacosamide (C₁₃H₁₈N₂O₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Mobile phase, Diluent 1, Diluent 2, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.001 mg/mL of USP Lacosamide RS in Diluent 1

Standard solution: 0.002 mg/mL of USP Lacosamide RS in Diluent 1

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 0.37, 0.47, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 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: Sample solution and Standard solution

Calculate the percentage of each degradation product in the portion of Tablets 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 0.10%.

Any individual unspecified degradation product: NMT 0.20%

Total degradation products: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and 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