Flecainide Acetate

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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C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂     474.39

Benzamide, N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)-, monoacetate;

N-(2-Piperidylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide monoacetate CAS RN®: 54143-56-5; UNII: M8U465Q1WQ.

1 DEFINITION

Flecainide Acetate contains NLT 98.0% and NMT 102.0% of flecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂), calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy〈197〉: [Note—Methods described in 〈197K〉 or 〈197A〉 may be used.]

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Solution: 130 µg/mL in alcohol

Analytical wavelength: 298 nm

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%.

C. 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: 0.1 M ammonium acetate in water. Adjust with acetic acid to a pH of 5.4.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (25:75)

Standard solution: 0.2 mg/mL of USP Flecainide Acetate RS in Diluent. Sonication may be needed for complete dissolution. Sample solution: 0.2 mg/mL of Flecainide Acetate in Diluent. Sonication may be needed for complete dissolution.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 300 nm

Column: 3.0-mm × 15-cm; 3-µm packing L1

Flow rate: 0.5 mL/min

Injection volume: 10 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of flecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂) in the portion of Flecainide Acetate taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of flecainide from the Sample solution

r_S = peak response of flecainide from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 OTHER COMPONENTS

Content of Acetate

Sample solution: Dissolve about 600 mg of Flecainide Acetate in about 100 mL of dimethylformamide, and stir by mechanical means until dissolved.

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N tetrabutylammonium hydroxide VS

Endpoint detection: Potentiometric

Analysis: Perform a blank determination and make any necessary correction. Each mL of 0.1 N tetrabutylammonium hydroxide is equivalent to 6.005 mg of acetic acid (C₂H₄O₂).

Acceptance criteria: 12.4%–12.8% on the dried basis

5 IMPURITIES

Residue on ignition 〈281〉: NMT 0.2%

Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay. System suitability solution: 0.25 mg/mL of USP Flecainide Acetate RS and 0.1 mg/mL of flecainide acid in Diluent Sensitivity solution: 0.001 mg/mL of USP Flecainide Acetate RS in Diluent

Standard solution: 0.01 mg/mL each of USP Flecainide Acetate RS and USP Flecainide Related Compound A RS in Diluent Sample solution: 2.0 mg/mL of Flecainide Acetate in Diluent. Sonication may be needed for complete dissolution.

System suitability

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

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

Suitability requirements

Resolution: NLT 5.0 between flecainide acetate and flecainide acid, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 50, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of flecainide related compound A in the portion of Flecainide Acetate taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of flecainide related compound A from the Sample solution

r_S = peak response of flecainide related compound A from the Standard solution

C_S = concentration of USP Flecainide Related Compound A RS in the Standard solution (mg/mL)

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

Calculate the percentage of each specified or unspecified impurity in the portion of Flecainide Acetate taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of flecainide acetate from the Standard solution

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

C_U = concentration of Flecainide Acetate 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 2,5-Bis(2,2,2-triuoroethoxy)benzoic acid.

^b N-(Pyridin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide.

6 SPECIFIC TESTS

Loss on drying 〈731〉

Analysis: Dry under vacuum at a pressure not exceeding 5 mm of mercury at 60° for 2 h.

Acceptance criteria: NMT 0.5%

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

Change to read:

USP Reference standards 〈11〉

USP Flecainide Acetate RS

USP Flecainide Related Compound A RS

3-[2,5-Bis(2,2,2-triuoroethoxy)phenyl]-1,5,6,7,8,8a-hexahydroimidazo[1,5-a]pyridine hydrochloride.

C₁₇H₁₈F₆N₂O₂ · HCl    432.79 (CN 1-Aug-2024)