(ben'' droe floo'' me thye' a zide).
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 [73-48-3].
Bendroflumethiazide contains NLT 98.0% and NMT 102.0% of C15H14F3N3O4S2, calculated on the anhydrous basis.
• A. Infrared Absorption 197K
Sample: Previously dried over silica gel for 4 h
Acceptance criteria: Meets the requirements
• B. Ultraviolet Absorption 197U
Analytical wavelength: 271 nm
Sample solution: 10 µg/mL in methanol
Acceptance criteria: Absorptivities, calculated on the anhydrous basis, do not differ by more than 4.0%.
Sample solution: Mix 5 mL of dilute hydrochloric acid (50% v/v) with 20 mg of Bendroflumethiazide, boil gently for 1 min, and cool in an ice bath.
Analysis: To the Sample solution add, in succession, 0.5 mL of sodium nitrite solution (1 mg/mL), 0.5 mL of ammonium sulfamate solution (5 mg/mL), and 0.5 mL of N-(1-naphthyl)ethylenediamine dihydrochloride solution (1 mg/mL).
Acceptance criteria: A deep red color is produced.
Sample: 190 mg of Bendroflumethiazide
Analysis: Dissolve the Sample in 80 mL of pyridine in a tall-form, 250-mL beaker in a well-ventilated hood. Add 3 drops of a saturated solution of azo violet in methanol, cover the beaker, and gently bubble nitrogen through the solution for 5 min, being careful to avoid any contact between the solution and the cover. Raise the nitrogen delivery tube above the solution surface and, maintaining a gentle flushing with nitrogen and stirring with a magnetic or mechanical stirring device, add 0.1 N sodium methoxide VS from a 10-mL buret inserted through an opening in the cover. Titrate to a blue endpoint, approaching the endpoint at a rate of 1 or 2 drop/s. Perform a blank determination, and make any necessary correction (see Titrimetry 541). Each mL of 0.1 N sodium methoxide is equivalent to 21.07 mg of C15H14F3N3O4S2.
Acceptance criteria: 98.0%102.0% on the anhydrous basis
• Residue on Ignition 281: NMT 0.2%
• Heavy Metals, Method II 231: 20 ppm
• 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).
• Limit of 2,4-Disulfamyl-5-trifluoromethylaniline
[NoteUse 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
Detector: UV 270 nm
Column: 4.6-mm × 30-cm; packing L11
Column temperature: 35 ± 5
Flow rate: 1.5 mL/min
Injection size: 20 µL
Sample: Standard solution
Resolution: NLT 1.4 between the methanol and 2,4-disulfamyl-5-trifluoromethylaniline peaks
Relative standard deviation: NMT 3.0% for five replicate injections
Samples: Standard solution and Sample solution
Calculate the percentage of 2,4-disulfamyl-5-trifluoromethylaniline in the portion of Bendroflumethiazide taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria: NMT 1.5%
• Water Determination, Method I 921: NMT 0.5%
• Packaging and Storage: Preserve in tight containers.
• USP Reference Standards 11
USP 2,4-Disulfamyl-5-trifluoromethylaniline RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2315