Propafenone Hydrochloride

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

Propafenone Hydrochloride contains NLT 98.0% and NMT 102.0% of C₂₁H₂₇NO₃ · HCl, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. Dissolve 0.5 g of Propafenone Hydrochloride in 50 mL of water with heating. Adjust with 0.1 N sodium hydroxide to a pH of 9.5–10.0: a precipitate is formed. Cool the mixture, and filter. Add 1 mL of 6 N nitric acid and 2–3 drops of 0.1 N silver nitrate to the filtrate: a precipitate is formed, which dissolves upon the addition of a few drops of ammonium hydroxide.

3 ASSAY

Procedure

Sample solution: Transfer 250 mg of Propafenone Hydrochloride to a 125-mL flask. Dissolve in 30 mL of methanol, and add 15 mL of mercuric acetate TS.

Analysis: Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction (see Titrimetry 〈541〉). Each mL of 0.1 N perchloric acid is equivalent to 37.79 mg of C₂₁H₂₇NO₃ · HCl.

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

IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Procedure

Solvent A: 3.42 g/L of dipotassium hydrogen phosphate trihydrate. Adjust with phosphoric acid to a pH of 2.5.

Solvent B: Acetonitrile

Mobile phase: See the gradient table below.

Diluent: Solvent A and Solvent B (13:7)

System suitability solution:

0.1 mg/mL of USP Propafenone Hydrochloride RS and USP Propafenone Related Compound B RS in Diluent

Standard solution:

0.001 mg/mL of USP Propafenone Hydrochloride RS in Diluent

Sample solution:

1 mg/mL of Propafenone Hydrochloride in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 1 mL/min

Injection size: 20 µL

Run time: NLT six times the retention time of propafenone

Suitability requirements

Resolution: NLT 3 between propafenone and propafenone related compound B

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Propafenone Hydrochloride taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response for each impurity from the Sample solution

rₛ = peak response of propafenone from the Standard solution

Cₛ = concentration of USP Propafenone Hydrochloride RS in the Standard solution

Cᵤ = concentration of Propafenone Hydrochloride in the Sample solution

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.3%.

[Note—Disregard any peak below 0.03%.]

Impurity Table 1

a (2E)-1-[2-[(2RS)-2-Hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylprop-2-en-1-one.

b 1-[2-[(2RS)-2,3-Dihydroxypropoxy]phenyl]-3-phenylpropan-1-one.

c 1,1′-[Propyliminobis(2-hydroxypropane-3,1-diyl)oxy-2,1-phenylene]bis(3-phenylpropan-1-one).

d 1-[2-[[(2RS)-Oxiranyl]methoxy]phenyl]-3-phenylpropan-1-one.

e 1,1′-[2-Hydroxypropane-1,3-diylbis(oxy-2,1-phenylene)]bis(3-phenylpropan-1-one).

4 SPECIFIC TESTS

Clarity of Solution: Dissolve 1.0 g in 30 mL of hot water, and observe without delay: the solution initially is clear.

Melting Range or Temperature 〈741〉: 171°–175°

pH 〈791〉: 5.0–6.2, in a solution (1 in 200)

Loss on Drying 〈731〉: Dry a sample at 105° to constant weight: it loses NMT 0.5% of its weight.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store at a temperature between 15° and 30°.

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.

C₂₁H₂₅NO₃ 339.43