Dofetilide

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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C₁₉H₂₇N₃O₅S₂      441.56

Methanesulfonamide, N-[4-[2-[methyl[2-[4-[(methylsulfon yl)amino]phenoxy]ethyl]amino]ethyl]phenyl]-;N-{4-[2-(Methyl{2-[4-(methylsulfonamido)phenoxy]ethyl}amino)ethyl]phenyl}methanesulfonamide _{(ERR 1-Nov-2022)} CAS RN: 115256-11-6; UNII: R4Z9X1N2ND.

1 DEFINITION

Dofetilide contains NLT 97.0% and NMT 103.0% of C,H,NOS, calculated on the anhydrous, solvent-free basis. 19 27

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

B. 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

Potassium hydroxide solution: 0.56 g/mL of potassium hydroxide

Buffer: 1.36 g of monobasic potassium phosphate and 5 mg of ascorbic acid in 1 L of water. Adjust with Potassium hydroxide solution to a pH of 7.0.

Mobile phase: Acetonitrile and Buffer (1:3)

System suitability solution: 25 µg/mL of USP Dofetilide RS and 0.5 µg/mL of USP Dofetilide Related Compound A RS in Mobile phase

Standard solution: 25 µg/mL of USP Dofetilide RS in Mobile phase

Sample solution: 25 µg/mL of Dofetilide in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 3.9-mm x 15-cm; 4-um packing L7

Temperature: 30°

Flow rate: 1 mL/min

Injection size: 50 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 8.0 between dofetilide and dofetilide related compound A, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₉H₂₇N₃O₅S₂, in the portion of Dofetilide taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of dofetilide from the Sample solution

r_s = peak response of dofetilide from the Standard solution

C_s = concentration of dofetilide in the Standard solution (µg/mL)

C_u = concentration of Dofetilide in the Sample solution (µg/mL)

Acceptance criteria: 97.0%–103.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Procedure

Buffer: 0.78 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 5.0 ± 0.1.

Diluent: Acetonitrile and Buffer (3:22)

Solution A: Buffer

Solution B: Methanol

Mobile phase: See the gradient table below

System suitability solution: 1.25 µg/mL each of USP Dofetilide RS and USP Dofetilide Related Compound A RS in Diluent

Standard solution: 1.25 µg/mL of USP Dofetilide RS in Diluent

Diluted standard solution: 0.125 µg/mL of USP Dofetilide RS in Diluent from the Standard solution

Sample solution: 0.25 mg/mL of Dofetilide in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 3.9-mm × 15-cm; 5-µm packing L1

Temperature: 30°

Flow rate: 1 mL/min

Injection size: 50 µL

System suitability

Samples: System suitability solution and Diluted standard solution

System suitability requirements

Resolution: NLT 5.0 between dofetilide and dofetilide related compound A, System suitability solution

Column eciency: NLT 35,000 theoretical plates for the dofetilide peak, System suitability solution

Tailing factor: NMT 1.5 for the dofetilide peak, System suitability solution

Relative standard deviation: NMT 10.0%, Diluted standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Dofetilide taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response for each impurity from the Sample solution

r_s = peak response of dofetilide from the Standard solution

C_s = concentration of USP Dofetilide RS in the Standard solution (mg/mL)

C_u = concentration of Dofetilide in the Sample solution (mg/mL)

F = relative response factor (see Impurity Table 1)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: See Impurity Table 1.

Impurity Table 1

^a N-[4-(2-(2-[4-(Methanesulfonamido)phenoxy]ethylamino)ethyl)phenyl]methanesulfonamide.

^b Unless otherwise determined.

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Dofetilide RS

USP Dofetilide Related Compound A RS

N-[4-(2-{2-[4-(Methanesulfonamido)phenoxy]ethylamino}ethyl)phenyl]methanesulfonamide.

      427.54