Bendroflumethiazide

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₁₅H₁₄F₃N₃O₄S₂  421.41

2H-1,2,4-Benzothiadiazine-7-sulfonamide, 3,4-dihydro-3-(phenylmethyl)-6-(trifluoromethyl)-, 1,1-dioxide, (±)-;

(+)-3-Benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide CAS RN^®: 73-48-3; ▲UNII: 5Q52X6ICJI. (USP 1-Dec-2021)

1 DEFINITION

Bendroflumethiazide contains NLT 98.0% and NMT 102.0% of bendroflumethiazide (C₁₅H₁₄F₃N₃O₄S₂), calculated on the anhydrous basis.

2 IDENTIFICATION

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

3.1 PROCEDURE

Use low-actinic glassware for the Standard solution and the Sample solution, and use the solutions within 30 min of preparation.

Diluent: Methanol and water (80:20)

Mobile phase: Dissolve 5.62 g of sodium chloride and 1.97 g of anhydrous sodium sulfate in 1000 mL of water in a 2-L volumetric flask. Add 4.0 mL of glacial acetic acid and 800 mL of methanol, and dilute with water to volume.

Standard solution: 0.05 mg/mL of USP Bendroflumethiazide RS in Diluent

Sample solution: 0.05 mg/mL of Bendroflumethiazide in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm x 15-cm; 5-µm packing L11

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of bendroflumethiazide

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bendroflumethiazide (C₁₅H₁₄F₃N₃O₄S₂) in the portion of Bendroflumethiazide taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of bendroflumethiazide from the Sample solution

r_S = peak response of bendroflumethiazide from the Standard solution s

C_S = concentration of USP Bendroflumethiazide RS in the Standard solution (mg/mL)

C_U = concentration of Bendroflumethiazide in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.2%

Delete the following:

4.2 SELENIUM (291)

Sample: 100 mg of Bendroflumethiazide and 100 mg of magnesium oxide

Acceptance criteria: The absorbance from the Test Solution is NMT one-half that from the Standard Solution (NMT 30 ppm). (USP 1-Dec-2021)

4.3 LIMIT OF 2,4-DISULFAMYL-5-TRIFLUOROMETHYLANILINE

Use low-actinic glassware for the Standard solution and the Sample solution.

Mobile phase: Dissolve 5.62 g of sodium chloride and 1.97 g of anhydrous sodium sulfate in 1000 mL of water in a 2-L volumetric flask. Add 4.0 mL of glacial acetic acid and 800 mL of methanol, and dilute with water to volume.

Standard solution: 0.75 µg/mL of USP 2,4-Disulfamyl-5-trifluoromethylaniline RS in methanol

Sample solution: 50 µg/mL of Bendroflumethiazide in methanol

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm x 30-cm; packing L11

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.4 between the methanol and 2,4-disulfamyl-5-trifluoromethylaniline peaks

Relative standard deviation: NMT 3.0% for 5 replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 2,4-disulfamyl-5-trifluoromethylaniline in the portion of Bendroflumethiazide taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of 2,4-disulfamyl-5-trifluoromethylaniline from the Sample solution

r_S = peak response of 2,4-disulfamyl-5-trifluoromethylaniline from the Standard solution

C_S = concentration of USP 2,4-Disulfamyl-5-trifluoromethylaniline RS in the Standard solution (µg/mL)

C_U = concentration of Bendroflumethiazide in the Sample solution (µg/mL)

Acceptance criteria: NMT 1.5%

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method I: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

Change to read:

USP REFERENCE STANDARDS (11)

USP Bendroflumethiazide RS

USP 2,4-Disulfamyl-5-trifluoromethylaniline RS

4-Amino-6-(trifluoromethyl) benzene-1,3-disulfonamide.

C₇H₈F₃N₃O₄S₂  319.28 (USP 1-Dec-2021)