Hydroflumethiazide

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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C₈H₈F₃N₃O₄S₂ 331.29 

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

3,4-Dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide CAS RN®: 135-09-1; UNII: 501CFL162R. 

1 DEFINITION 

Hydroflumethiazide contains NLT 98.0% and NMT 102.0% of hydroflumethiazide (C₈H₈F₃N₃O₄S₂), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read: 

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U 

Sample solution: 10 µg/mL of hydroflumethiazide in methanol 

Standard solution: 10 µg/mL of USP hydroflumethiazide RS in methanol 

Acceptance criteria: Meets the requirements 

3 ASSAY 

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Procedure 

Standard solution: 10 µg/mL of USP hydroflumethiazide RS in methanol 

Sample solution: 10 µg/mL of hydroflumethiazide in methanol 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

Mode: UV 

Analytical wavelength: Maximum absorbance at about 273 nm 

Cell: 1 cm 

Blank: methanol 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of hydroflumethiazide (C₈H₈F₃N₃O₄S₂) in the portion of hydroflumethiazide taken: 

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Hydroflumethiazide RS in the Standard solution (μg/mL)

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

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

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 1.0% 

Delete the following: 

Selenium 〈291〉: NMT 0.003%

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Diazotizable Substances 

Dilute hydrochloric acid: Hydrochloric acid (1 in 5) 

Sodium nitrite solution: Sodium nitrite (1 in 100), freshly prepared 

Ammonium sulfamate solution: Ammonium sulfamate (1 in 10), freshly prepared 

N-(1-naphthyl)ethylenediamine dihydrochloride solution: N-(1-naphthyl)ethylenediamine dihydrochloride (1 in 1000), freshly prepared Standard stock solution: 200 µg/mL of USP 2,4-Disulfamyl-5-trifluoromethylaniline RS in acetone 

Standard solution: 20 µg/mL of USP 2,4-Disulfamyl-5-trifluoromethylaniline RS in water from Standard stock solution Sample solution: Transfer 100 mg of hydroflumethiazide to a 50-mL volumetric flask, dissolve in 5 mL of acetone, and dilute with water to volume. 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: Vis 

Analytical wavelength: 518 nm 

Cell: 1 cm 

Blank: Acetone in water (1 in 10) 

Analysis 

Samples: Standard solution, Sample solution, and Blank 

Transfer 5.0 mL each of the Standard solution, Sample solution, and Blank to separate 25-mL volumetric flasks. To each flask add 2.0 mL of Dilute hydrochloric acid, and immediately add 1 mL of Sodium nitrite solution. Mix, and allow to stand for 5 min. Add 1 mL of Ammonium sulfamate solution to each flask, mix, and allow to stand for 1 min, with frequent swirling. Add 1 mL of N-(1- naphthyl)ethylenediamine dihydrochloride solution, and mix. After 1 min, dilute with water to volume, and mix. Concomitantly, and within 5 min after mixing, taking care to establish the same elapsed time for each solution, determine the absorbances of the solutions. 

Acceptance criteria: The absorbance of the solution from the Sample solution does not exceed that of the Standard solution, corresponding to NMT 1.0% of diazotizable substances. 

5 SPECIFIC TESTS 

Melting Range or Temperature 〈741〉, Class I: 270°–275° 

pH 〈791〉 

Sample solution: 1 in 100 dispersion in water 

Acceptance criteria: 4.5–7.5 

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

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers. 

USP Reference Standards 〈11〉 

USP 2,4-Disulfamyl-5-trifluoromethylaniline RS  C₈H₈F₃N₃O₄S₂     319.29 

USP hydroflumethiazide RS