Dronedarone 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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N-{2-Butyl-3-[4-(3-dibutylaminopropoxy)benzoyl] benzofuran-5-yl}methanesulfonamide, hydrochloride;

Methanesulfonamide, N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]-, monohydrochloride CAS RN^®: 141625-93-6; UNII: FA36DV299Q.

1 DEFINITION

Dronedarone Hydrochloride contains NLT 98.0% and NMT 101.5% of dronedarone hydrochloride, calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A.SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscoov: 197K (CN 1 M-2020): Meets the requirements

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

C. IDENTIFICATION TESTS GENERAL, Chloride: 191)

Sample solution: Dissolve 100 mg of Dronedarone Hydrochloride in 8 ml of methanol and dilute with water to 10.0 mL. Use 2.0 mL for the analysis.

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Buffer: Combine 2.0 ml. of triethylamine with 1 L of water and adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (50:50)

System suitability stock solution: 1 mg/mL each of USP Dronedarone Hydrochloride RS, and USP. Dronedarone Related Compound. A.RS in methanol

System suitability solution: 0.01 mg/mL each of USP Dronedarone Hydrochloride RS and USP Dronedarone Related Compound A RS in

Mobile phase from System suitability stock solution

Standard solution: 0.1 mg/ml, of USP Dronedarone Hydrochloride RS in Mobile phase

Sample solution: 0.1 mg/mL of Dronedarone Hydrochloride in Mobile phase

Chromatographic system

Mode: LC

Detector: UV 288 nm

Column: 4.6-mm x 25-cm; 5-um packing L10

Flow rate: 0.8 mL/min

Injection volume: 20 µL

Run time: NLT 2.15 times the retention time of dronedarone

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for dronedarone related compound A and dronedarone are 0.71 and 1.0, respectively.

Suitability requirements

Resolution: NLT 8 between dronedarone and dronedarone related compound A, System suitability solution

Tailing factor: 0.8-2.2 for dronedarone, System suitability solution

Relative standard deviation: NMT 0.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of dronedarone hydrochloride (C₃₁H₄₄N₂O₅S · HCl) in the portion of Dronedarone Hydrochloride taken

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

r_U = peak response of dronedarone from the Sample solution

r_S = peak response of dronedarone from the Standard solution

C_S = concentration of USP Dronedarone Hydrochloride RS in the Standard solutionn (mg/ml)

C_U = nominal concentration of of dronedarone in the Sample sulation (mg/ml)

Acceptance criteria: 98.0%-101.5% on the anhydrous and solvent-free basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

Solution A: Combine 2 ml, of triethylamine with 950 ml of water. Adjust with phosphoric acid to a pH of 4.0 and then dilute with water to 1 L.

Solution B: Acetonitrile

Mobile phase: See Table 1. (Not Collect data for 58 min.

Diluent: Acetonitrile and Solution A, 50:50

Standard stock solution: 0.2 mg/mL of USP Dronedarone Hydrochloride RS and 0.4 mg/mL of USP Dronedarone Related Compound A RS. respectively, in methanol

Standard solution: 2 μg/mL of USP Dronedarone Hydrochloride RS and 4mu*g / m * L of USP Dronedarone Related Compound A RS, respectively, in Diluent from the Standard stock solution

Sensitivity solution: 1mu*g / m * L of USP Dronedarone Hydrochloride RS and 2mu*g / m * L of USP Dronedarone Related Compound ABS in Diluent from the Standard solution

Sample solution: 2 mg/mL of Dronedarone Hydrochloride in Diluent. Sonicate for 5 min to dissolve completely. Pass through a suitable filter of 0.45-μm pore size.

Chromatographic system

Mode: LC

Detector: UV 246 nm

Column: 4.6-mm x 25 cm; 5-µm packing L10

Flow rate: 0.8 mL/min

Injection volume: 25 µL

System suitability

Samples: Standard solution and Sensitivity solution

[Nor-The relative retention times for dronedarone related compound A and dronedarone are 0.58 and 1.00, respectively.)

Suitability requirements

Resolution: NLT 25 between dronedarone and dronedarone related compound A, Standard solution

Signal-to-noise ratio: NLT 10 for dronedarone and NLT 20 for dronedarone related compound A, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of dronedarone related compound A in the portion of Dronedarone Hydrochloride taken:

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

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

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

C_S = concentration of USP Dronedarone Hydrochloride RS in the Standard solutionn (mg/ml)

C_U = concentration of Dronedarone Hydrochloride in the Sample solation (mg/ml)

Calculate the percentage of any unspecified impurity in the portion of Dronedarone Hydrochloride taken:

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

r_U = peak response of any unspecied impurity from the Sample solution

r_S = peak response of dronedarone from the Standard solution

C_S = concentration of USP Dronedarone Hydrochloride RS in the Standard solutionn (mg/ml)

C_U = concentration of Dronedarone Hydrochloride in the Sample solation (mg/ml)

Acceptance criteria: Disregard peaks below 0.05%.

Dronedarone related compound A: NMT 0.15%

Any unspecified impurity: NMT 0.10%

Total impurities: NMT 0.3%

5 SPECIFIC TESTS

WATER DETERMINATION. Method Jn(921): NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Protect from light and store at room temperature.