Diflunisal
;)
[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 98.0percent and not more than 101.5percent of C13H8F2O3,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:
Infrared Absorption á197Mñ.
B:
Ultraviolet Absorption á197Uñ—
Solution:
40µg per mL.
Medium:
hydrochloric acid in methanol (1in 120).
Absorptivities at 315nm,calculated on the dried basis,do not differ by more than 3.0%.
Loss on drying á731ñ—
Dry it in vacuum at a pressure not exceeding 5mm of mercury at 60
for 4hours:it loses not more than 0.3%of its weight.
for 4hours:it loses not more than 0.3%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
0.001%.
Chromatographic purity—
Prepare a solution of it in methanol containing about 10mg per mL.Prepare solutions of USP Diflunisal RSin methanol having concentrations of 10,0.05,and 0.02mg per mL,respectively (Standard solutions A,B,and C).Apply 5-µLportions of all four solutions to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)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 UVlight:the chromatograms show principal spots at about the same RFvalue.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 Band 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 Vá467ñ:
meets the requirements.
Solvent—
Use dimethyl sulfoxide.
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 18minutes.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Dissolve an accurately weighed quantity of USP Diflunisal RSin a mixture of acetonitrile and water (4:1)to obtain a solution having a known concentration of about 1mg 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 0.2mg per mL.
Assay preparation—
Transfer about 50mg of Diflunisal,accurately weighed,to a 50-mLvolumetric flask.Dilute with a mixture of acetonitrile and water (4:1)to volume,and mix.Transfer 5.0mLof this solution to a 25-mLvolumetric flask.Dilute with a mixture of acetonitrile and water (1:1)to volume,and mix.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1and is maintained at a temperature of 40.The flow rate is about 1.5mLper 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 2500theoretical 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%.
.The flow rate is about 1.5mLper 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 2500theoretical 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 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C13H8F2O3in the portion of Diflunisal taken by the formula:
250C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Diflunisal RSin the Standard preparation,and rUand rSare the peak responses of the major peaks obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 639
Phone Number:1-301-816-8139