Hydroflumethiazide Tablets
»Hydroflumethiazide Tablets contain not less than 95.0percent and not more than 105.0percent of the labeled amount of hydroflumethiazide (C8H8F3N3O4S2).
Packaging and storage— Preserve in tight containers.
Identification— Finely powder a number of Tablets,equivalent to about 100mg of hydroflumethiazide,and place the powder in a 35-mL,screw-capped centrifuge tube.Add 30mLof acetone,cap the tube,and allow it to stand for 30minutes,with occasional shaking.Centrifuge,and decant the supernatant into a 100-mLbeaker.Evaporate on a steam bath to dryness,add 10mLof sodium hydroxide solution (1in 250)to the residue,and mix.Transfer the liquid to a 125-mLseparator.Rinse the beaker with 5mLof water,and add the rinsing to the main portion.Add 50mLof anhydrous ethyl ether to the separator,insert the stopper,shake vigorously for 2minutes,releasing pressure as necessary,and allow the phases to separate.Draw off the lower phase,retaining any emulsion in the separator,and pass it through a membrane filter having a 0.2-to 2-µm porality.Add dilute hydrochloric acid (1in 10)dropwise to the filtrate in a 50-mLbeaker,stirring well and checking the pHwith wide-range test paper after each drop.[NOTE—Crystallization begins at about pH5.Rubbing the bottom of the beaker with a glass stirring rod helps to initiate crystallization.]When precipitation is complete,decant and discard the supernatant,and wash the precipitate with 5mLof water.Decant and discard the wash water,and dry the precipitate at 105for 30minutes:the IRspectrum of a potassium bromide dispersion of the dried material exhibits maxima only at the same wavelengths as that of a similar preparation of USP Hydroflumethiazide RS.
Dissolution á711ñ—
Medium: dilute hydrochloric acid (1in 100);900mL.
Apparatus 2: 50rpm.
Time: 60minutes.
Procedure— Determine the amount of C8H8F3N3O4S2dissolved from UVabsorbances at the wavelength of maximum absorbance at about 273nm of filtered portions of the solution under test,suitably diluted with Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Hydroflumethiazide RSin the same medium.
Tolerances— Not less than 80%(Q)of the labeled amount of C8H8F3N3O4S2is dissolved in 60minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Procedure for content uniformity— Crush 1Tablet and quantitatively transfer to a 100-mLvolumetric flask,add about 50-mLof methanol,and shake until disintegration is complete.Dilute with methanol to volume,mix,and filter,discarding the first 20mLof the filtrate.Dilute a portion of the subsequent filtrate with methanol to obtain a solution containing approximately 10µg of hydroflumethiazide per mL.Concomitantly determine the absorbances of this solution and of a Standard solution of USP Hydroflumethiazide RS,in the same medium having a known concentration of about 10µg per mLin 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 Tablet taken by the formula:
(TC/D)(AU/AS),
in which Tis the labeled quantity,in mg,of hydroflumethiazide in the Tablet,Cis the concentration,in µg per mL,of USP Hydroflumethiazide RSin the Standard solution,Dis the concentration,in µg per mL,of hydroflumethiazide in the test solution,based upon the labeled quantity per Tablet and the extent of dilution,and AUand ASare the absorbances of the solution from the Tablet and the Standard solution,respectively.
Assay—
Standard preparation— Transfer about 30mg of USP Hydroflumethiazide RS,accurately weighed,to a 100-mLvolumetric flask,add sodium hydroxide solution (1in 100)to volume,and mix.Transfer 5.0mLof this solution to a second 100-mLvolumetric flask,dilute with sodium hydroxide solution (1in 100)to volume,and mix.The concentration of USP Hydroflumethiazide RSin the Standard preparationis about 15µg per mL.
Chromatographic column— Proceed as directed for Column Partition Chromatographyunder Chromatography á621ñ,packing a chromatographic tube with two segments of packing material.The lower segment is a mixture of 1g of Solid Supportand 1mLof sodium hydroxide solution (1in 100),and the upper segment is a mixture prepared as directed under Assay preparation.
Assay preparation— Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 75mg of hydroflumethiazide,to a 50-mLvolumetric flask,add about 35mLof sodium hydroxide solution (1in 100),shake vigorously,dilute with sodium hydroxide solution (1in 100)to volume,and mix.Mix 2.0mLof this solution with 3g of Solid Supportas directed under Chromatographic column,and transfer to the column.Wash the column with 50mLof water-saturated chloroform,then with 50mLof water-saturated ether,and discard the eluates.Elute the hydroflumethiazide from the column with 100mLof glacial acetic acid in ether (1in 1000),collecting the eluate in a 250-mLseparator.Add 100mLof a 1in 1000solution of glacial acetic acid in ether to a second 250-mLseparator to provide a blank,and treat each as follows:Add 60mLof isooctane to each separator,mix,and extract the resulting solution with three 50-mLportions of sodium hydroxide solution (1in 100),collecting the extracts in a 200-mLvolumetric flask.Dilute with sodium hydroxide solution (1in 100)to volume,and mix.
Procedure— Concomitantly determine the absorbances of the solutions in 1-cm cells at the wavelength of maximum absorbance at about 273nm,with a suitable spectrophotometer,using the blank.Calculate the quantity,in mg,of hydroflumethiazide (C8H8F3N3O4S2)in the portion of Tablets taken by the formula:
5C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Hydroflumethiazide RSin the Standard preparation;and AUand ASare the absorbances of the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 971
Phone Number:1-301-816-8305