Bendroflumethiazide
421.422H-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 not less than 98.0 percent and not more than 102.0 percent of C15H14F3N3O4S2, calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
USP Reference standards 
11
—
USP Bendroflumethiazide RS.
USP 2,4-Disulfamyl-5-trifluoromethylaniline RS.
11—
USP Bendroflumethiazide RS.
USP 2,4-Disulfamyl-5-trifluoromethylaniline RS.
Identification—
A:
Infrared Absorption 197K: previously dried over silica gel for 4 hours.
197K: previously dried over silica gel for 4 hours.
B:
Ultraviolet Absorption 197U—
197U—
Solution:
10 µg per mL.
Medium:
methanol.
Absorptivities at 271 nm, calculated on the anhydrous basis, do not differ by more than 4.0%.
C:
Mix 5 mL of dilute hydrochloric acid (1 in 2) with 20 mg of Bendroflumethiazide, boil gently for 1 minute, and cool in an ice bath. Add in succession 0.5 mL of sodium nitrite solution (1 in 1000), 0.5 mL of ammonium sulfamate solution (1 in 200), and 0.5 mL of N-(1-naphthyl)ethylenediamine dihydrochloride solution (1 in 1000): a deep red color is produced.
Water, Method I 921:
not more than 0.5%.
921:
not more than 0.5%.
Residue on ignition 281:
not more than 0.2%.
281:
not more than 0.2%.
Heavy metals, Method II 231:
0.002%.
231:
0.002%.
Selenium 291—
The absorbance from the Test Solution prepared with 100 mg of Bendroflumethiazide and 100 mg of magnesium oxide, is not greater than one-half that from the Standard Solution (0.003%).
291—
The absorbance from the Test Solution prepared with 100 mg of Bendroflumethiazide and 100 mg of magnesium oxide, is not greater than one-half that from the Standard Solution (0.003%).
Limit of 2,4-disulfamyl-5-trifluoromethylaniline—
[note—Use low-actinic glassware for the Test preparation and the Standard preparation.]
Mobile phase—
Dissolve 5.62 g of sodium chloride and 1.97 g of anhydrous sodium acetate in 1000 mL of water in a 2-liter volumetric flask. Add 4.0 mL of glacial acetic acid and 800 mL of methanol, dilute with water to volume, mix, filter, and degas.
Standard preparation—
Dissolve an accurately weighed quantity of USP 2,4-Disulfamyl-5-trifluoromethylaniline RS in methanol to obtain a solution having a known concentration of about 0.75 µg per mL.
Test preparation—
Transfer about 25 mg of Bendroflumethiazide, accurately weighed, to a 100-mL volumetric flask, add methanol to volume, and mix. Transfer 10.0 mL of this solution to a 50-mL volumetric flask, dilute with methanol to volume, and mix.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 270-nm detector and a 4.6-mm × 30-cm column that contains packing L11 maintained at a temperature of 35 ± 5
. The flow rate is about 1.5 mL per minute. Chromatograph five replicate injections of the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation is not more than 3.0%, and the resolution factor between the methanol and 2,4-disulfamyl-5-trifluoromethylaniline is not less than 1.4.
621)—The liquid chromatograph is equipped with a 270-nm detector and a 4.6-mm × 30-cm column that contains packing L11 maintained at a temperature of 35 ± 5. The flow rate is about 1.5 mL per minute. Chromatograph five replicate injections of the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation is not more than 3.0%, and the resolution factor between the methanol and 2,4-disulfamyl-5-trifluoromethylaniline is not less than 1.4.
Procedure—
Separately inject equal volumes (about 20 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the peak response of the 2,4-disulfamyl-5-trifluoromethylaniline. Calculate the percentage of 2,4-disulfamyl-5-trifluoromethylaniline in the portion of Bendroflumethiazide taken by the formula:
100(CS / CU)(rU / rS)
in which CS is the concentration, in µg per mL, of USP 2,4-Disulfamyl-5-trifluoromethylaniline RS in the Standard preparation; CU is the concentration, in µg per mL, of bendroflumethiazide in the Test preparation; and rU and rS are the peak responses obtained from the Test preparation and the Standard preparation, respectively. Not more than 1.5% of 2,4-disulfamyl-5-trifluoromethylaniline is found.
Assay—
Dissolve about 190 mg of Bendroflumethiazide, accurately weighed, in 80 mL of pyridine in a 250-mL, tall-form 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 minutes, 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 drops per second. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N sodium methoxide is equivalent to 21.07 mg of C15H14F3N3O4S2.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Sujatha Ramakrishna, Ph.D.
Scientist 1-301-816-8349 |
(MDCV05) Monograph Development-Cardiovascular |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
USP32–NF27 Page 1636
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.