(ben'' droe floo'' me thye' a zide).
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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     [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%.
•  C.
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.
•  Procedure
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%
•  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
[Note—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 
Mode:  LC
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
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 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
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP 2,4-Disulfamyl-5-trifluoromethylaniline RS in the Standard solution (µg/mL)
CU== concentration of Bendroflumethiazide in the Sample solution (µg/mL)
Acceptance criteria:  NMT 1.5%
•  Packaging and Storage: Preserve in tight containers.
•  USP Reference Standards 11
USP Bendroflumethiazide RS Click to View Structure
USP 2,4-Disulfamyl-5-trifluoromethylaniline RS
    C7H8F3N3O4S2         319.29
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Topic/Question Contact Expert Committee
Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
(SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
USP35–NF30 Page 2315