Flecainide Acetate 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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1 DEFINITION

Flecainide Acetate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of flecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂).

2 IDENTIFICATION

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

B. The UV spectrum 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

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: Lactic acid and water (2:98)

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

Sample stock solution: Nominally 1 mg/mL of flecainide acetate in Diluent prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask, add Diluent to about 80% of the flask capacity, and sonicate for 30 min. Dilute with Diluent to volume.

Sample solution: Nominally 0.2 mg/mL of flecainide acetate from the Sample stock solution in Diluent. Centrifuge and use the supernatant.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 300 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Flow rate: 0.5 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of flecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂) in the portion of Tablets 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 = nominal concentration of flecainide acetate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Test 1 (CN 1-Dec-2024)

Medium: 0.075 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min for Tablets each containing 50 mg of flecainide acetate; or 60 min for 100-, 150-, or 200-mg Tablets

Standard solution: A known concentration of USP Flecainide Acetate RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium to a concentration that is similar to that of the Standard solution.

Instrumental conditions

Mode: UV-Vis

Analytical wavelength: 296 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of flecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂) dissolved.

Tolerances: NLT 70% (Q) of the labeled amount of flecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂) is dissolved from 50-mg Tablets in 30 min; or

from 100-, 150-, or 200-mg Tablets in 60 min.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: 0.2 mg/mL of USP Flecainide Acetate RS prepared as follows. Dissolve a suitable amount of USP Flecainide Acetate RS in 2.5% of flask volume of methanol and dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter, discarding an appropriate volume of filtrate so that a consistent result can be obtained. Dilute with Medium, if necessary, to a concentration similar to that of the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 296 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of

ecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂) dissolved:

Result = (A_U /A_S ) × C_S × V × D × (1/L) × 100

A_U = absorbance from the Sample solution

A_S = absorbance from the Standard solution

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

V = volume of Medium, 500 mL

D = dilution factor of the Sample solution, if needed

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of flecainide acetate (C₁₇H₂₀F₆N₂O₃ · C₂H₄O₂) is dissolved. (CN 1-Dec-2024)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

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: 0.002 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: Nominally 2 mg/mL of flecainide acetate in Diluent prepared as follows. Transfer NLT 5 Tablets to a suitable volumetric flask, add Diluent to about 80% of the flask capacity, and sonicate for 30 min. Dilute with Diluent to volume. Centrifuge a portion of the solution and use the supernatant.

System suitability

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

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

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

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

Calculate the percentage of any unspecified degradation product in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecified degradation product 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 = nominal concentration of flecainide acetate in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

^a 2,5-Bis(2,2,2-trifluoroethoxy)benzoic acid.

^b Included for identification only. These impurities are controlled in the drug substance. They are not to be reported for the drug product and should not be included in the total impurities.

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light. Store at controlled room temperature.

Change to read:

USP Reference standards 〈11〉

USP Flecainide Acetate RS

USP Flecainide Related Compound A RS

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

C₁₇H₁₈F₆N₂O₂ · HCl 432.79