Torsemide Tablets

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

Torsemide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of torsemide (C₁₆H₂₀N₄O₃S).

2 IDENTIFICATION

A. The 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.

3 ASSAY

Change to read:

3.1 Procedure

Buffer: 2.72 g/L of monobasic potassium phosphate

Solution A: Acetonitrile and methanol (10:90)

Mobile phase: Buffer and Solution A (50:50). Adjust with diluted phosphoric acid (1 in 10 v/v) to a pH of 4.0.

Standard solution: 0.4 mg/mL of USP Torsemide RS prepared as follows. To a quantity of USP Torsemide RS in a suitable flask, add methanol to 30% of the flask volume and sonicate for NLT 8 min. Add Buffer to fill 75% of the flask volume, cool, and dilute with Mobile phase. Pass through a membrane filter of 0.45-µm pore size.

Sample solution: Nominally 0.4 mg/mL of torsemide prepared as follows. Place 40 mg of torsemide from NLT 20 powdered Tablets in a 100-mL volumetric flask. Add methanol to 30% of the flask volume and sonicate for NLT 8 min. Add Buffer to fill 75% of the flask volume, cool, and dilute with Mobile phase. Pass through a membrane filter of 0.45-µm pore size. The Sample solution is not stable at room temperature but is stable for 12 h at 6°.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 288 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
• Column: 4.6-mm × 15-cm; 5-µm packing L1
• Temperatures
• Autosampler: 6°
• Column: 30°
• Flow rate: 1 mL/min
• Injection volume: 20 µL
• Run time: NLT 2 times the retention time of torsemide

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 1.5
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of torsemide (C₁₆H₂₀N₄O₃S) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of torsemide from the Sample solution

rₛ = peak response of torsemide from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 Dissolution 〈711〉

4.1.1 Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Buffer, Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard stock solution: 0.55 mg/mL of USP Torsemide RS prepared as follows. Transfer a quantity of USP Torsemide RS to a suitable volumetric flask. Add methanol to 30% of the flask volume and sonicate until dissolved. Add Buffer to fill 75% of the flask volume, cool to room temperature, and dilute with Mobile phase to volume.

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the label claim in mg/Tablet.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of torsemide (C₁₆H₂₀N₄O₃S) dissolved:

Result = (rᵤ/rₛ) × (Cₛ/L) × V × 100

rᵤ = peak response of torsemide from the Sample solution

rₛ = peak response of torsemide from the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of torsemide (C₁₆H₂₀N₄O₃S) is dissolved.

4.1.2 Test 2 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard stock solution: 0.11 mg/mL of USP Torsemide RS in Medium

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the label claim in mg/Tablet.

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

• (See Ultraviolet-Visible Spectroscopy 〈857〉.)
• Mode: UV
• Analytical wavelength: 285 nm
• Cell: 1.0 cm for 5-, 10-, and 20-mg Tablets and 0.1 cm for 100-mg Tablets
• Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of torsemide (C₁₆H₂₀N₄O₃S) dissolved:

Result = (Aᵤ/Aₛ) × (Cₛ/L) × V × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of torsemide (C₁₆H₂₀N₄O₃S) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements.

5 IMPURITIES

Change to read:

5.1 Organic Impurities

Buffer and Solution A: Prepare as directed in the Assay.

Mobile phase: Buffer and Solution A (55:45). Adjust with diluted phosphoric acid (1 in 10 v/v) to a pH of 4.0.

Standard stock solution A: 0.1 mg/mL of USP Torsemide Related Compound A RS and 0.02 mg/mL of USP Torsemide Related Compound E RS prepared as follows. Dissolve a suitable quantity each of USP Torsemide Related Compound A RS and USP Torsemide Related Compound E RS in methanol to 32% of the flask volume and sonicate to dissolve. Dilute with Mobile phase to volume.

System suitability solution: 0.4 mg/mL of USP Torsemide RS, 4 µg/mL of USP Torsemide Related Compound A RS, and 0.8 µg/mL of USP Torsemide Related Compound E RS prepared as follows. To a quantity of USP Torsemide RS in a suitable flask add methanol to 30% of the flask volume and sonicate to dissolve. Add Buffer to fill 75% of the flask volume, and cool. Add a suitable volume of Standard stock solution A and dilute with Mobile phase to volume.

Standard stock solution B: 0.4 mg/mL each of USP Torsemide RS prepared as follows. To a suitable amount of USP Torsemide RS in a suitable flask, add methanol to 30% of the flask volume and sonicate for NLT 8 min. Add Buffer to fill 75% of the flask volume, cool, and dilute with Mobile phase to volume.

Sensitivity solution: 0.4 µg/mL of USP Torsemide RS in Mobile phase from Standard stock solution B

Standard solution: 4 µg/mL each of USP Torsemide RS and USP Torsemide Related Compound A RS and 0.8 µg/mL of USP Torsemide Related Compound E RS in Mobile phase from Standard stock solution A and Standard stock solution B

Sample solution: Nominally 0.4 mg/mL of torsemide prepared as follows. Weigh 40 mg of torsemide from NLT 20 powdered Tablets into a 100-mL volumetric flask. Add methanol to 30% of the flask volume, mix, and sonicate for NLT 8 min. Add Buffer to fill 75% of the flask volume, cool to room temperature, dilute with Mobile phase to volume, and mix. The Sample solution is not stable at room temperature, but is stable for 15 h at 6°.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 288 nm
• Column: 4.6-mm × 15-cm; 3.5-µm packing L1
• Autosampler temperature: 6°
• Flow rate: 0.8 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution, Sensitivity solution, and Standard solution
• [Note-See Table 1 for relative retention times.]
• Suitability requirements
• Resolution: NLT 2.5 between torsemide related compound A and torsemide related compound E, System suitability solution
• Tailing factor: NMT 2.0 for the torsemide peak, System suitability solution
• Relative standard deviation: NMT 5.0% for the torsemide peak, Standard solution
• Signal-to-noise ratio: NLT 10.0, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of torsemide related compound A or torsemide related compound E in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of torsemide related compound A or torsemide related compound E from the Sample solution

rₛ = peak response of torsemide related compound A or torsemide related compound E from the Standard solution

Cₛ = concentration of USP Torsemide Related Compound A RS or USP Torsemide Related Compound E RS in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified degradation product in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any unspecified degradation product from the Sample solution

rₛ = peak response of torsemide from the Standard solution

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

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

Acceptance criteria: See Table 1.

Table 1

ᵃ N-(Ethylcarbamoyl)-4-(3-tolylamino)pyridine-3-sulfonamide. 

ᵇ Process-related impurity controlled in the drug substance. 

ᶜ Ethyl {[4-(3-tolylamino)pyridin-3-yl]sulfonyl}carbamate.

ᵈ N-(Butylcarbamoyl)-4-(3-tolylamino)pyridine-3-sulfonamide. 

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers and store at controlled room temperature.

Labeling: The labeling indicates the Dissolution test with which the product complies, if Test 1 is not used.

Change to read:

USP Reference Standards 〈11〉

USP Torsemide RS

USP Torsemide Related Compound A RS

4-[(3-Methylphenyl)amino]-3-pyridinesulfonamide.

C₁₂H₁₃N₃O₂S 263.32

USP Torsemide Related Compound E RS

4-(3-Tolyl)-2H-pyrido[4,3-e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxide.

C₁₃H₁₁N₃O₃S 289.31