Ibutilide Fumarate

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

Ibutilide Fumarate contains NLT 98.0% and NMT 102.0% of ibutilide fumarate [(C₂₀H₃₆N₂O₄S)·C₄H₄O₄], calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

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

Solution A: 2 mL/L of triethylamine in water. Adjust with perchloric acid to a pH of 2.5.

Mobile phase: Acetonitrile and Solution A (40:60)

Standard solution: 0.2 mg/mL of USP Ibutilide Fumarate RS in Mobile phase.

[Note—Sonication may be necessary for complete dissolution.]

Sample solution: 0.2 mg/mL of Ibutilide Fumarate in Mobile phase.

[Note—Sonication may be necessary for complete dissolution.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 227 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

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

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ibutilide fumarate [(C₂₀H₃₆N₂O₄S)·C₄H₄O₄] in the portion of Ibutilide Fumarate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of ibutilide from the Sample solution

rₛ = peak response of ibutilide from the Standard solution

Cₛ = concentration of USP Ibutilide Fumarate RS in the Standard solution (mg/mL)

Cᵤ = concentration of Ibutilide Fumarate in the Sample solution (mg/mL)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.20%

Content of Fumaric Acid

Solution A, Mobile phase, and Sample solution: Proceed as directed in the Assay.

Chromatographic system: Proceed as directed in the Assay, except use a UV detector at 207 nm.

Standard stock solution: 0.2 mg/mL of USP Fumaric Acid RS in Mobile phase.

[Note—Sonication may be necessary for complete dissolution.]

Standard solution: 0.02 mg/mL of USP Fumaric Acid RS in Mobile phase

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of fumaric acid content in the portion of Ibutilide Fumarate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of fumaric acid from the Sample solution

rₛ = peak response of fumaric acid from the Standard solution

Cₛ = concentration of USP Fumaric Acid RS in the Standard solution (mg/mL)

Cᵤ = concentration of Ibutilide Fumarate in the Sample solution (mg/mL)

Acceptance criteria: 12.7%–13.5%

Organic Impurities

Solution A: 2 mL/L of triethylamine in water. Adjust with perchloric acid to a pH of 2.5.

Solution B: Acetonitrile

Diluent: Acetonitrile and Solution A (40:60)

Mobile phase: See Table 1.

Table 1

Standard solution: 2 µg/mL of USP Ibutilide Fumarate RS and 3 µg/mL each of USP Ibutilide Related Compound A RS and USP Ibutilide Related Compound B RS in Diluent

Sample solution: 2 mg/mL of Ibutilide Fumarate in Diluent

Chromatographic system: Proceed as directed in the Assay, except use a run time of NLT 2.5 times the retention time of ibutilide for the Standard solution and NLT 6.2 times the retention time of ibutilide for the Sample solution.

System suitability

Sample: Standard solution

Suitability requirements

Column e￾ciency: NLT 5000 theoretical plates for the ibutilide peak [Ký tự không đọc được]

Relative standard deviation: NMT 3.0% for the ibutilide peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ibutilide related compound A, ibutilide related compound B, and any unspeci￾ed impurity in the portion of Ibutilide Fumarate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of ibutilide related compound A, ibutilide related compound B, or any other unspeci￾ed impurity from the Sample solution

rₛ = peak response of ibutilide related compound A, ibutilide related compound B, or ibutilide (for calculating any other unspeci￾ed impurity) from the Standard solution

Cₛ = concentration of USP Ibutilide Related Compound A RS, USP Ibutilide Related Compound B RS, or USP Ibutilide Fumarate RS (for calculating any unspeci￾ed impurity) in the Standard solution (mg/mL)

Cᵤ = concentration of Ibutilide Fumarate in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard the fumaric acid peak and any peak less than 0.01%.

Table 2

ᵃ This impurity is controlled in the test for Content of Fumaric Acid.

ᵇ N-Ethyl-N-heptyl-4-hydroxy-4-[4-(methylsulfonamido)phenyl]butanamide.

ᶜ N-Ethyl-N-heptyl-4-[4-(methylsulfonamido)phenyl]-4-oxobutanamide.

5 SPECIFIC TESTS

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in air-tight containers, and protect from light. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Fumaric Acid RS

USP Ibutilide Fumarate RS

USP Ibutilide Related Compound A RS

N-Ethyl-N-heptyl-4-[4-(methylsulfonamido)phenyl]-4-oxobutanamide.

C₂₀H₃₂N₂O₄S 396.54

USP Ibutilide Related Compound B RS

N-Ethyl-N-heptyl-4-hydroxy-4-[4-(methylsulfonamido)phenyl]butanamide.

C₂₀H₃₄N₂O₄S 398.56