Lacosamide

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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C₁₃H₁₈N₂O₃  250.30

Propanamide, 2-(acetylamino)-3-methoxy-N-(phenylmethyl)-, (2R)-;

(+)-(R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide. CAS RN®: 175481-36-4.

1 DEFINITION

Lacosamide contains NLT 98.0% and NMT 102.0% of lacosamide (C₁₃H₁₈N₂O₃).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K or 197A

B. The retention time of the major peak of the Sample solution corresponds to that of the System suitability solution, as obtained in the test for Limit of Lacosamide S-Enantiomer.

3 ASSAY

Procedure

Solution A: To each liter of water add 1 mL of trifluoroacetic acid.

Solution B: Acetonitrile and methanol (50:50). To each liter add 0.3 mL of trifluoroacetic acid.

Mobile phase: See Table 1.

Table 1

System suitability solution: 5 mg/mL of USP Lacosamide RS and 10 μg/mL each of USP Lacosamide Related Compound B RS and N- benzylacetamide prepared as follows. Weigh an appropriate amount of USP Lacosamide RS, USP Lacosamide Related Compound B RS, and N-benzylacetamide into a suitable volumetric flask. Dissolve in 10% of the flask volume of methanol. Dilute with water to volume.

Standard solution: 5 mg/mL of USP Lacosamide RS prepared as follows. Weigh an appropriate amount of USP Lacosamide RS into a suitable volumetric flask. Dissolve in 10% of the flask volume of methanol. Dilute with water to volume.

Sample solution: 5 mg/mL of Lacosamide prepared as follows. Weigh an appropriate amount of Lacosamide into a suitable volumetric flask.

Dissolve in 10% of the flask volume of methanol. Dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 258 nm

Column: 4.6-mm × 15-cm; 3.5-μm packing L7

Autosampler temperature: 10°

Flow rate: 1.2 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between N-benzylacetamide and lacosamide; NLT 4.5 between lacosamide and lacosamide related compound B,

System suitability solution

Tailing factor: NMT 2.5, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lacosamide (C₁₃H₁₈N₂O₃) in the portion of Lacosamide taken:

Result = (r_U/r_S) × (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 the USP Lacosamide RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Limit of Lacosamide S-Enantiomer

Mobile phase: Heptane, isopropyl alcohol, and water (90: 10: 0.3)

System suitability solution: 1 mg/mL of USP Lacosamide RS and 5 μg/mL of USP Lacosamide S-Enantiomer RS in Mobile phase

Sample solution: 1 mg/mL of Lacosamide in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; 10-μm packing L51

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 1.7 times the retention time of lacosamide

System suitability

Sample: System suitability solution

[Note—The relative retention times for lacosamide S-enantiomer and lacosamide are 0.75 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between lacosamide S-enantiomer and lacosamide

Signal-to-noise ratio: NLT 10 for S-enantiomer

Analysis

Sample: Sample solution

Calculate the percentage of S-enantiomer in the portion of Lacosamide taken:

Result = (r /r ) × 100

r = peak response of S-enantiomer

r = sum of the peak responses of lacosamide and S-enantiomer

Acceptance criteria: NMT 0.15%

Organic Impurities

Solution A, Solution B, Mobile phase, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Diluent: Methanol and water (10:90)

Sensitivity solution: 2.5 μg/mL of USP Lacosamide RS in Diluent

Standard solution: 0.005 mg/mL of USP Lacosamide RS in Diluent

System suitability

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

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between N-benzylacetamide and lacosamide; NLT 4.5 between lacosamide and lacosamide related compound B, 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 impurity in the portion of Lacosamide taken:

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

r_U = peak response of each impurity 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 = concentration of Lacosamide in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

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

^b (R)-N-Benzyl-3-methoxy-2-(N-methylacetamido)propanamide.

^c (R)-N-Benzyl-2-(3-benzylureido)-3-methoxypropanamide.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.2%. [Note—Method Ia or Method Ic may be used.]

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 B RS

2-Acetamido-3-(benzylamino)-3-oxopropyl acetate.

C₁₈H₁₄N₂O₄ 278.31

USP Lacosamide S-Enantiomer RS

(S)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide.

C₁₃H₁₈N₂O₃ 250.29 (USP 1-May-2021)