Nadolol and Bendroflumethiazide Tablets
»Nadolol and Bendroflumethiazide Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amounts of nadolol (C17H27NO4)and bendroflumethiazide (C15H14F3N3O4S2).
Packaging and storage Preserve in tight containers.
USP Reference standards á11ñ USP Bendroflumethiazide RS.USP2,4-Disulfamyl-5-trifluoromethylaniline RS.USP Nadolol RS.
Identification The retention times of the major peaks in the chromatogram of the Assay preparationcorrespond to those of the Standard preparationobtained as directed in the Assay.
Dissolution,Procedure for a Pooled Sample á711ñ [NOTEProtect solutions from light throughout this test.]
Medium: 0.1Nhydrochloric acid;900mL.
Apparatus 2: 50rpm.
Procedure Determine the amounts of C17H27NO4and C15H14F3N3O4S2dissolved,employing the procedure set forth in the Assay,using filtered portions of the solution under test,suitably diluted with Medium,if necessary,in comparison with a Standard solution having known concentrations of USP Nadolol RSand USP Bendroflumethiazide RS,prepared by dissolving them in the minimal amount of methanol and diluting to the desired concentrations with Medium.
Tolerances Not less than 80%(Q)of the labeled amounts of nadolol (C17H27NO4)and bendroflumethiazide (C15H14F3N3O4S2)are dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements for Content uniformitywith respect to both nadolol and bendroflumethiazide.
Assay [NOTEUse low-actinic glassware for the Assay preparationand the Standard preparation.]
Mobile phase Dissolve 5.62g of sodium chloride and 1.97g of anhydrous sodium acetate in 1000mLof water in a 2-liter volumetric flask.Add 4.0mLof glacial acetic acid and 800mLof methanol,dilute with water to volume,mix,filter,and degas.Make adjustments,if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation Dissolve accurately weighed quantities of USP Nadolol RSand USP Bendroflumethiazide RSin methanol and dilute quantitatively,and stepwise if necessary,with methanol to obtain a solution having known concentrations of about 0.4mg of USP Nadolol RSper mLand about 0.4Jmg of USP Bendroflumethiazide RSper mL,Jbeing the ratio of the labeled amount,in mg,of bendroflumethiazide to the labeled amount,in mg,of nadolol per Tablet.
Assay preparation Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 40mg of nadolol,to a 100-mLvolumetric flask,add methanol and sonicate for 15minutes with occasional shaking.Dilute with methanol to volume,mix,and centrifuge.
System suitability preparation Prepare a solution in methanol containing about 0.4mg each of USP Nadolol RSand USP2,4-Disulfamyl-5-trifluoromethylaniline RSper mL.
Chromatographic system (see Chromatography á621ñ)The liquid chromatograph is equipped with a 270-nm detector and a 4.6-mm ×30-cm column that contains packing L11.The flow rate is about 1.5mLper minute.Chromatograph the System suitability preparationand the Standard preparation,and record the peak responses as directed under Procedure:the resolution,R,between the solvent and 2,4-disulfamyl-5-trifluoromethylaniline peaks is not less than 1.4,the resolution,R,between the 2,4-disulfamyl-5-trifluoromethylaniline and nadolol peaks is not less than 1.4,and the resolution,R,between the nadolol and bendroflumethiazide peaks is not less than 1.7.The relative standard deviation for replicate injections of the Standard preparationis not more than 3.0%.
Procedure Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses of the major peaks.The relative retention times are about 0.3for nadolol and 1.0for bendroflumethiazide.Calculate the quantity,in mg,of nadolol (C17H27NO4)in the portion of Tablets taken by the formula:
100C(rU/rS),in which Cis the concentration,in mg per mL,of USP Nadolol RSin the Standard preparation,and rUand rSare the peak responses of nadolol obtained from the Assay preparationand the Standard preparation,respectively.Calculate the quantity,in mg,of bendroflumethiazide (C15H14F3N3O4S2)in the portion of Tablets taken by the same formula,changing the terms to refer to bendroflumethiazide.
Auxiliary Information Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28NF23Page 1322Pharmacopeial Forum:Volume No.30(1)Page 132