Propafenone Hydrochloride Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Propafenone Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of propafenone hydrochloride (C₂₁H₂₇NO₃·HCl).

2 IDENTIFICATION

Change to read:

A. The ▲2S (USP41) retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Add the following:

▲B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲2S (USP41)

3 ASSAY

Change to read:

Procedure

Buffer: 0.1 M monobasic potassium phosphate prepared as follows. Dissolve 13.6 g of monobasic potassium phosphate in 900 mL of water, adjust with phosphoric acid to a pH of 3.1, and then dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (32:68)

Standard solution: 0.15 mg/mL of USP Propafenone Hydrochloride RS in Mobile phase

Sample stock solution: Nominally 1.5 mg/mL of propafenone hydrochloride ▲2S (USP41) in Mobile phase prepared as follows. ▲Transfer an appropriate quantity of propafenone hydrochloride from NLT 20 powdered Tablets to a suitable volumetric flask, and▲2S (USP41) add Mobile phase to ▲2S (USP41) 90% of the total volume. Sonicate for 10 min. Cool to room temperature, and dilute with Mobile phase to volume. Stir for 10 min, pass through a suitable filter of 0.45-µm pore size, and discard the first 5 mL of the filtrate.

Sample solution: Nominally 0.15 mg/mL of propafenone hydrochloride from Sample stock solution in Mobile phase. Pass through a suitable filter of 0.45-µm pore size, and discard the first 5 mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm. ▲For Identification B, use a diode array detector in the range of 200–400 nm.▲2S (USP41)

Column: 4.6-mm × 15-cm; 5-µm packing L7

Column temperature: 45°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

Run time: NLT 3 times the retention time of the propafenone peak

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of propafenone hydrochloride (C₂₁H₂₇NO₃·HCl) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of propafenone from the Sample solution

rₛ = peak response of propafenone from the Standard solution

Cₛ = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of propafenone hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Standard solution: 0.17 mg/mL of USP Propafenone Hydrochloride RS in 0.1 N hydrochloric acid prepared as follows. To a suitable quantity of USP Propafenone Hydrochloride RS in a suitable volumetric flask, add 0.1 N hydrochloric acid to fill 75% of the total volume. Place the flask in a water bath at 37° with stirring until completely dissolved. Remove the flask from the water bath, cool to room temperature, and dilute with 0.1 N hydrochloric acid to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and discard the first 5 mL of the filtrate.

Instrumental conditions

Mode: UV

Analytical wavelength: 250 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of propafenone hydrochloride (C₂₁H₂₇NO₃·HCl) dissolved:

Result = (Aᵤ / Aₛ) × (C / L) × V × 100

Aᵤ = absorbance of propafenone from the Sample solution

Aₛ = absorbance of propafenone from the Standard solution

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

L = label claim for propafenone hydrochloride (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of propafenone hydrochloride (C₂₁H₂₇NO₃·HCl) is dissolved.

Change to read:

Uniformity of Dosage Units 〈905〉: Meet the requirements ▲2S (USP41)

5 IMPURITIES

Change to read:

Organic Impurities

Solution A: 2.61 g/L of dipotassium hydrogen phosphate in water. Adjust with phosphoric acid to a pH of 2.5.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Solution A and Solution B (65:35)

System suitability solution: 0.1 mg/mL each of USP Propafenone Hydrochloride RS and USP Propafenone Related Compound B RS in Diluent

▲Standard stock solution: 0.05 mg/mL each of USP Propafenone Hydrochloride RS and USP Propafenone Related Compound B RS in Diluent▲2S (USP41)

Standard solution: 1 µg/mL each of USP Propafenone Hydrochloride RS and USP Propafenone Related Compound B RS ▲from Standard stock solution▲2S (USP41) in Diluent

Sample solution: Nominally 1 mg/mL of propafenone hydrochloride in Diluent prepared ▲as follows. Transfer an appropriate quantity of propafenone hydrochloride from NLT 20 powdered Tablets to a suitable volumetric flask, and▲2S (USP41) add Diluent to ▲2S (USP41) 90% of the total volume, sonicate for 10 min, and cool to room temperature. Dilute with Diluent to volume, and stir for 10 min. Pass through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 5-µm packing L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

▲[Note—See Table 2 for relative retention times.]▲2S (USP41)

Suitability requirements

Resolution: NLT 3.0 between propafenone and propafenone related compound B, System suitability solution

Tailing factor: NMT 2.0 for the propafenone peak, Standard solution

Relative standard deviation: NMT 5.0% for the propafenone ▲and propafenone related compound B peaks,▲2S (USP41) Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of propafenone related compound B in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of propafenone related compound B from the Sample solution

rₛ = peak response of propafenone related compound B from the Standard solution

Cₛ = concentration of USP Propafenone Related Compound B RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of propafenone hydrochloride in the Sample solution (µg/mL)

Calculate the percentage of dealkyl propafenone and any ▲unspecified degradation product▲2S (USP41) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of dealkyl propafenone or any ▲unspecified degradation product▲2S (USP41) from the Sample solution

rₛ = peak response of propafenone from the Standard solution

Cₛ = concentration of USP Propafenone Hydrochloride RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of propafenone hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 2.

Table 2

ᵃ 2′-(2-Hydroxy-3-aminopropoxy)-3-phenylpropiophenone.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store at controlled room temperature in tightly closed containers at a relative humidity below 60%.

Change to read:

USP Reference Standards 〈11〉

USP Propafenone Hydrochloride RS

USP Propafenone Related Compound B RS

▲(RS,E)-1-[2-[2-Hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylprop-2-en-1-one.▲2S (USP41)

C₂₁H₂₅NO₃ 339.43