Nadolol and Bendroflumethiazide Tablets
» Nadolol and Bendroflumethiazide Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of nadolol (C17H27NO4) and bendroflumethiazide (C15H14F3N3O4S2).
Packaging and storage Preserve in tight containers.
USP Reference standards 11
USP 2,4-Disulfamyl-5-trifluoromethylaniline RS
Identification The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those of the Standard preparation obtained as directed in the Assay.
Dissolution, Procedure for a Pooled Sample 711 [noteProtect solutions from light throughout this test. ]
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure Determine the amounts of C17H27NO4 and C15H14F3N3O4S2 dissolved, 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 RS and 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 30 minutes.
Uniformity of dosage units 905: meet the requirements for Content uniformity with respect to both nadolol and bendroflumethiazide.
Assay [noteUse low-actinic glassware for the Assay 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. Make adjustments, if necessary (see System Suitability under Chromatography 621).
Standard preparation Dissolve accurately weighed quantities of USP Nadolol RS and USP Bendroflumethiazide RS in methanol and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having known concentrations of about 0.4 mg of USP Nadolol RS per mL and about 0.4J mg of USP Bendroflumethiazide RS per mL, J being 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 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 40 mg of nadolol, to a 100-mL volumetric flask, add methanol and sonicate for 15 minutes with occasional shaking. Dilute with methanol to volume, mix, and centrifuge.
System suitability preparation Prepare a solution in methanol containing about 0.4 mg each of USP Nadolol RS and USP 2,4-Disulfamyl-5-trifluoromethylaniline RS per mL.
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. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability preparation and 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 preparation is not more than 3.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses of the major peaks. The relative retention times are about 0.3 for nadolol and 1.0 for bendroflumethiazide. Calculate the quantity, in mg, of nadolol (C17H27NO4) in the portion of Tablets taken by the formula:
100C(rU / rS)in which C is the concentration, in mg per mL, of USP Nadolol RS in the Standard preparation, and rU and rS are the peak responses of nadolol obtained from the Assay preparation and 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.
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USP35NF30 Page 3979Pharmacopeial Forum: Volume No. 30(1) Page 132