(Ph. Eur. monograph 0370)
C15H14F3N3O4S2 421.4 73-48-3
Action and use
Thiazide diuretic.
Preparations
Bendroflumethiazide Tablets
Bendroflumethiazide Oral Suspension
DEFINITION
(3RS)-3-Benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.
Content
98.0 per cent to 102.0 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder
Solubility
Practically insoluble in water, freely soluble in acetone, soluble in ethanol (96 per cent).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison bendroflumethiazide CRS.
TESTS
Related substances
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.
Solvent mixture Mix 40 volumes of methanol R and 60 volumes of a 2.0 g/L solution of citric acid monohydrate R.
Test solution Dissolve 10.0 mg of the substance to be examined in the solvent mixture and dilute to 50.0 mL with the solvent mixture.
Reference solution (a) Dissolve 2 mg of bendroflumethiazide impurity A CRS and 2.5 mg of altizide CRS in the solvent mixture and dilute to 10 mL with the solvent mixture. Mix 1 mL of this solution with 1 mL of the test solution and dilute to 100 mL with the solvent mixture.
Reference solution (b) Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.
Column:
— size: l = 0.15 m, Ø = 3.0 mm;
— stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 μm);
— temperature: 40 °C.
Mobile phase: Mix 15 volumes of tetrahydrofuran R, 25 volumes of methanol R and 60 volumes of a 2.0 g/L solution of citric acid monohydrate R.
Flow rate: 0.8 mL/min.
Detection: Spectrophotometer at 273 nm.
Injection: 20 μL.
Run time: Twice the retention time of bendroflumethiazide.
Relative retention: With reference to bendroflumethiazide (retention time = about 8 min): impurity A = about 0.2; altizide = about 0.5.
System suitability: Reference solution (a):
— resolution: minimum 10 between the peaks due to altizide and bendroflumethiazide.
Limits:
— impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.1 per cent);
— unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);
— total: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);
— disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 °C.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.150 g in 50 mL of dimethyl sulfoxide R. Titrate to the 2 point of inflexion with 0.1 M tetrabutylammonium hydroxide in 2-propanol, determining the end-point potentiometrically (2.2.20). Carry out a blank titration.
1 mL of 0.1 M tetrabutylammonium hydroxide in 2-propanol is equivalent to 21.07 mg of C15H14F3N3O4S2.
IMPURITIES
Specified impurities A.
A. 4-amino-6-(trifluoromethyl)benzene-1,3-disulfonamide.
