Hydroflumethiazide
;)
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 [135-09-1].
»Hydroflumethiazide contains not less than 98.0percent and not more than 102.0percent of C8H8F3N3O4S2,calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
USP Reference standards á11ñ—
USP2,4-Disulfamyl-5-trifluoromethylaniline RS.USP Hydroflumethiazide RS.
Identification—
A:
Infrared Absorption á197Kñ,previously dried over silica gel for 4hours.
Solution:
10µg per mL.
Medium:
methanol.
and 275
pHá791ñ:
between 4.5and 7.5,in a 1in 100dispersion in water.
Water,Method Iá921ñ:
not more than 1.0%.
Residue on ignition á281ñ:
not more than 1.0%.
Heavy metals,Method IIá231ñ:
0.002%.
Selenium á291ñ:
0.003%.
Diazotizable substances—
Standard preparation—
Transfer 10.0mg of USP2,4-Disulfamyl-5-trifluoromethylaniline RSto a 50-mLvolumetric flask,dissolve in and dilute with acetone to volume,and mix.Transfer 10.0mLof this solution to a 100-mLvolumetric flask,dilute with water to volume,and mix.
Test preparation—
Transfer 100mg to a 50-mLvolumetric flask,dissolve in 5mLof acetone,dilute with water to volume,and mix.
Procedure—
Transfer 5.0mLeach of the Standard preparation,the Test preparation,and a solution of acetone in water (1in 10)to provide the blank,to separate 25-mLvolumetric flasks.To each flask add 2.0mLof dilute hydrochloric acid (1in 5),and immediately add 1mLof freshly prepared sodium nitrite solution (1in 100).Mix,and allow to stand for 5minutes.Add 1mLof freshly prepared ammonium sulfamate solution (1in 10)to each flask,mix,and allow to stand for 1minute,with frequent swirling.Add 1mLof a freshly prepared solution of N-(1-naphthyl)ethylenediamine dihydrochloride (1in 1000),and mix.After 1minute,dilute with water to volume,and mix.Concomitantly,and within 5minutes after mixing,taking care to establish the same elapsed time for each solution,determine the absorbances of the solutions in 1-cm cells at 518nm,with a suitable spectrophotometer,using the blank to set the instrument:the absorbance of the solution from the Test preparationdoes not exceed that of the solution from the Standard preparation,corresponding to not more than 1.0%of diazotizable substances.
Organic volatile impurities,Method Vá467ñ:
meets the requirements.
Solvent—
Use dimethyl sulfoxide.
Assay—
Transfer about 50mg of Hydroflumethiazide,accurately weighed,to a 100-mLvolumetric flask,add methanol to volume,and mix.Transfer 2.0mLof this solution to a second 100-mLvolumetric flask,dilute with methanol to volume,and mix.Concomitantly determine the absorbances of this solution and a Standard solution of USP Hydroflumethiazide RSin the same medium having a known concentration of about 10µg per mL,in 1-cm cells at the wavelength of maximum absorbance at about 273nm,with a suitable spectrophotometer,using methanol as the blank.Calculate the quantity,in mg,of C8H8F3N3O4S2in the Hydroflumethiazide taken by the formula:
5C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Hydroflumethiazide RSin the Standard solution;and AUand ASare the absorbances of the solution of Hydroflumethiazide and the Standard solution,respectively.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 970
Phone Number:1-301-816-8305