» Diflunisal Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C13H8F2O3.
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, obtained as directed in the Assay.
B: Transfer a quantity of finely ground Tablets, equivalent to about 100 mg of diflunisal, to a 10-mL volumetric flask, add 2 mL of water, and sonicate for 5 minutes. Dilute with methanol to volume, sonicate for an additional 5 minutes, mix, and filter. Separately apply 10 µL each of the filtrate and a Standard solution of USP Diflunisal RS in methanol solution (4 in 5) containing 10 mg per mL to a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Develop the chromatogram in a solvent system consisting of n-hexane, glacial acetic acid, and chloroform (17:3:2) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, air-dry, and examine under long-wavelength UV light: the RF value of the principal spot in the chromatogram of the test solution corresponds to that obtained from the Standard solution.
pH 7.20, 0.1 M Tris buffer Dissolve 121 g of tris(hydroxymethyl)aminomethane (THAM) in 9 liters of water. Adjust the solution with a 7 in 100 solution of anhydrous citric acid in water to a pH of 7.45, at 25. Dilute with water to 10.0 liters, equilibrate to 37, and adjust to a pH of 7.20, if necessary.
Medium: pH 7.20, 0.1 M Tris buffer; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure Determine the amount of C13H8F2O3 dissolved from UV absorbances at the wavelength of maximum absorbance at about 306 nm of filtered portions of the solution under test, suitably diluted with pH 7.20, 0.1 M Tris buffer, in comparison with a Standard solution having a known concentration of USP Diflunisal RS in the same Medium.
Tolerances Not less than 80% (Q) of the labeled amount of C13H8F2O3 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Procedure for content uniformity Transfer 1 finely powdered Tablet to a 200-mL volumetric flask, add 50 mL of water, shake by mechanical means for 30 minutes, and sonicate for 2 minutes. Add 100 mL of alcohol to the flask, shake by mechanical means for 15 minutes, and sonicate for 2 minutes. Dilute with alcohol to volume, mix, and centrifuge a portion of the solution. Quantitatively dilute an accurately measured volume of the resultant clear supernatant with alcohol, if necessary, to obtain a test solution containing about 1.25 mg per mL. Transfer about 125 mg of USP Diflunisal RS, accurately weighed, to a 100-mL volumetric flask, add 75 mL of alcohol to dissolve, dilute with water to volume, and mix to obtain the Standard solution. Transfer 3.0 mL each of the Standard solution and the test solution to separate 50-mL volumetric flasks. To each flask add 5.0 mL of a solution containing 1 g of ferric nitrate in 100 mL of 0.08 N nitric acid, dilute with water to volume, and mix. Concomitantly determine the absorbances of the solutions at the wavelength of maximum absorbance at about 550 nm, with a suitable spectrophotometer, using water as the blank. Calculate the quantity, in mg, of C13H8F2O3 in the Tablet by the formula:
(TC / D)(AU / AS)in which T is the labeled quantity, in mg, of diflunisal in the Tablet; C is the concentration, in µg per mL, of USP Diflunisal RS in the Standard solution; D is the concentration, in µg per mL, of diflunisal in the test solution, based upon the labeled quantity per Tablet and the extent of dilution; and AU and AS are the absorbances of the solutions from the test solution and the Standard solution, respectively.
Mobile phasePrepare a suitable degassed mixture of water, methanol, acetonitrile, and glacial acetic acid (45:40:17:6) such that the retention time of diflunisal is about 8 minutes.
Standard preparation Dissolve a suitable quantity of USP Diflunisal RS in a mixture of acetonitrile and water (60:40) to obtain a solution having a known concentration of about 1.0 mg per mL.
Assay preparation Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of diflunisal, to a 100-mL volumetric flask containing about 5 mL of water. Sonicate for 5 minutes, add 60.0 mL of acetonitrile, sonicate for an additional 5 minutes, dilute with water to volume, mix, and filter.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the analyte peak is not more than 2.0, and the relative standard deviation for replicate injections is not more than 2.0%.
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 for the major peaks. Calculate the quantity, in mg, of diflunisal (C13H8F2O3) in the portion of Tablets taken by the formula:
100C(rU / rS)in which C is the concentration, in mg per mL, of USP Diflunisal RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2899