Rufinamide

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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C₁₀H₈F₂N₄O 238.19

1H-1,2,3-Triazole-4-carboxamide, 1-[(2,6-difluorophenyl)methyl]-;

1-(2,6-Difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide CAS RN^®: 106308-44-5; UNII: WFW942PR79.

1 DEFINITION

Rufinamide contains NLT 98.0% and NMT 102.0% of C₁₀H₈F₂N₄O, calculated on the as-is basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

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

3.1 Procedure

Use amber glassware for all volumetric solutions.

Diluent: Methanol and tetrahydrofuran (50:50)

Mobile phase: Methanol, tetrahydrofuran, and water (12:5:83)

System suitability stock solution: 0.8 mg/mL of USP Rufinamide RS and 4 µg/mL each of USP Rufinamide Related Compound A RS and USP Rufinamide Related Compound B RS in Diluent.

[Note—USP Rufinamide Related Compound B RS is used for peak identification purposes only.]

System suitability solution: 0.2 mg/mL of USP Rufinamide RS and 0.8 µg/mL each of USP Rufinamide Related Compound A RS and USP Rufinamide Related Compound B RS in water from the System suitability stock solution

Standard stock solution: 0.8 mg/mL of USP Rufinamide RS in Diluent

Standard solution: 0.2 mg/mL of USP Rufinamide RS in water from the Standard stock solution

Sample stock solution: 0.8 mg/mL of Rufinamide in Diluent

Sample solution: 0.2 mg/mL of Rufinamide in water from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 12.5-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: 2.6 times the retention time of the rufinamide peak

System suitability

[Note—For relative retention times refer to Table 1 in Organic Impurities.]

Sample: System suitability solution

Suitability requirements

Tailing factor: NMT 1.2 for rufinamide

Resolution: NLT 2.5 between rufinamide and rufinamide related compound A

Relative standard deviation: NMT 1.0% for rufinamide and NMT 5.0% for rufinamide related compound A

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of rufinamide (C₁₀H₈F₂N₄O) in the portion of the sample 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 USP Rufinamide RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0% on the as-is basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Use amber glassware for all volumetric solutions.

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

Standard solution: 0.8 µg/mL of USP Rufinamide RS in water from the Standard stock solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of any individual impurity in the portion of Rufinamide taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of rufinamide from the Standard solution

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

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

Acceptance criteria: See Table 1.

Table 1

ᵃ 1-(2-Fluorobenzyl)-1H-1,2,3-triazole-4-carboxamide.

ᵇ Methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Rufinamide RS

USP Rufinamide Related Compound A RS

1-(2-Fluorobenzyl)-1H-1,2,3-triazole-4-carboxamide.

C₁₀H₉FN₄O 220.20

USP Rufinamide Related Compound B RS

Methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate.

C₁₁H₉F₂N₃O₂ 253.20