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Diflunisal
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C13H8F2O3 250.20

[1,1¢-Biphenyl]-3-carboxylic acid, 2¢,4¢-difluoro-4-hydroxy-.
2¢,4¢-Difluoro-4-hydroxy-3-biphenylcarboxylic acid [22494-42-4].
» Diflunisal contains not less than 98.0 percent and not more than 101.5 percent of C13H8F2O3, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification—
B: Ultraviolet Absorption 197U—
Solution: 40 µg per mL.
Medium: hydrochloric acid in methanol (1 in 120).
Absorptivities at 315 nm, calculated on the dried basis, do not differ by more than 3.0%.
Loss on drying 731— Dry it in vacuum at a pressure not exceeding 5 mm of mercury at 60 for 4 hours: it loses not more than 0.3% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.001%.
Chromatographic purity— Prepare a solution of it in methanol containing about 10 mg per mL. Prepare solutions of USP Diflunisal RS in methanol having concentrations of 10, 0.05, and 0.02 mg per mL, respectively (Standard solutions A, B, and C). Apply 5-µL portions of all four solutions to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture and previously washed with methanol. Allow the spots to dry, and develop the chromatogram in a freshly prepared solvent system consisting of a mixture of n-hexane, dioxane, and glacial acetic acid (85:10:5) in a paper-lined, equilibrated tank, until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, allow to air-dry, and examine the plate under short-wavelength UV light: the chromatograms show principal spots at about the same RF value. Estimate the concentration of any spot observed in the chromatogram of the test solution, other than the principal spot, by comparison with the spots in the chromatograms of Standard solutions B and C: the intensity of any individual spot is not greater than that of the principal spot obtained from Standard solution C (0.2%), and the sum of all additional spots is not greater than that of the principal spot obtained from Standard solution B (0.5%).
Organic volatile impurities, Method V 467: meets the requirements.
Solvent— Use dimethyl sulfoxide.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Mobile phase— Prepare a suitable mixture of water, methanol, acetonitrile, and glacial acetic acid (55:23:10:2) such that the retention time of diflunisal is about 18 minutes. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Diflunisal RS in a mixture of acetonitrile and water (4:1) to obtain a solution having a known concentration of about 1 mg per mL. Dilute an accurately measured volume of this solution with a mixture of acetonitrile and water (1:1) to obtain a solution having a known concentration of about 0.2 mg per mL.
Assay preparation— Transfer about 50 mg of Diflunisal, accurately weighed, to a 50-mL volumetric flask. Dilute with a mixture of acetonitrile and water (4:1) to volume, and mix. Transfer 5.0 mL of this solution to a 25-mL volumetric flask. Dilute with a mixture of acetonitrile and water (1:1) to volume, and mix.
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 and is maintained at a temperature of 40. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the column efficiency determined from the analyte peak is not less than 2500 theoretical plates, the tailing factor is not more than 2.0, the capacity factor is not less than 7.2, and the relative standard deviation for replicate injections is not more than 1%.
Procedure— Separately inject equal volumes (about 10 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 C13H8F2O3 in the portion of Diflunisal taken by the formula:
250C(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 of the major peaks obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Clydewyn M. Anthony, Ph.D., Scientist
Expert Committee : (MDCCA05) Monograph Development-Cough Cold and Analgesics
USP29–NF24 Page 697
Phone Number : 1-301-816-8139