Warfarin Sodium Tablets
»Warfarin Sodium Tablets contain not less than 95.0percent and not more than 105.0percent of the labeled amount of warfarin sodium (C19H15NaO4).
Packaging and storage Preserve in tight,light-resistant containers.
A: The retention time of the major peak obtained from the Assay preparationcorresponds to that obtained from the Standard preparation,both relative to the internal standard,obtained as directed in the Assay.
B: Infrared Absorption á197KñPrepare the test specimen as follows.Triturate a quantity of finely powdered Tablets,equivalent to about 200mg of warfarin sodium,with 50mLof water,centrifuge,and filter the supernatant.Extract with 50mLof ether,transfer the aqueous layer to a second separator,and discard the ether.Adjust with hydrochloric acid to a pHof less than 3,using short-range pHindicator paper,and extract with 50mLof chloroform.Transfer the chloroform layer to another separator,extract with 50mLof sodium hydroxide solution (1in 250),and discard the chloroform.Transfer the aqueous layer to a beaker,and adjust with hydrochloric acid to a pHof less than 3(using the pHindicator paper)to precipitate the warfarin.Stir the mixture and allow the precipitate to coagulate.Filter,and wash the precipitate with four 5-mLportions of water.If the precipitate is not white or practically white,dissolve it in a minimum volume of sodium hydroxide solution (1in 250),dilute with water to 50mL,and repeat the foregoing procedure,beginning with Extract with 50mLof ether.Dry the warfarin so obtained in vacuum over phosphorus pentoxide for 4hours.
Apparatus 2: 50rpm.
Mobile phase and Chromatographic systemProceed as directed in the Assay.
Internal standard solution Prepare a solution of propylparaben in water containing,in each mL,an amount of propylparaben equivalent to 0.0025times the labeled amount,in mg,of warfarin sodium in each Tablet.[NOTEAsmall amount of methanol may be used,if necessary,to dissolve the propylparaben.]
Standard stock solution Dissolve an accurately weighed quantity of USP Warfarin RSin water to obtain a solution having a known concentration of about 0.0011Lmg per mL,Lbeing the labeled amount,in mg,of warfarin sodium in the Tablets.[NOTEUse a small amount of 0.1Nsodium hydroxide to aid in dissolution.]
Standard solution To 3.0mLof Standard stock solution,add 1.0mLof Internal standard solution,and mix.
Test solution To a filtered 3.0-mLaliquot of the solution under test,add 1.0mLof Internal standard solution,and mix.
Procedure Separately inject equal volumes (about 40µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of warfarin sodium dissolved by the formula:
(330.32/308.34)(900C)(RU/RS),in which Cis the concentration,in mg per mL,of USP Warfarin RSin the Standard stock solution,330.32and 308.34are the molecular weights of warfarin sodium and warfarin,respectively;and RUand RSare the ratios of the peak responses of warfarin to those of propylparaben obtained from the Test solutionand the Standard solution,respectively.
Tolerances Not less than 80%(Q)of the labeled amount of C19H15NaO4is dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
pH7.4Buffer and Chromatographic systemProceed as directed in the Assayunder Warfarin Sodium.
Solvent mixture Prepare a mixture of pH7.4Bufferand acetonitrile (85:15).
Mobile phase Prepare a filtered and degassed mixture of methanol,water,and glacial acetic acid (68:32:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Internal standard solution Prepare a solution of propylparaben in acetonitrile having a concentration of 1mg per mL.
Standard preparation Transfer about 62.5mg of USP Warfarin RS,accurately weighed,to a 200-mLvolumetric flask,and dissolve in 78mLof 0.1Nsodium hydroxide.Add 50mLof 0.2Mmonobasic potassium phosphate,dilute with water to volume,and mix.Transfer 15.0mLof this solution to a 50-mLvolumetric flask.Add 5.0mLof Internal standard solution,and dilute with Solvent mixtureto volume.
Assay preparation Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 5mg of warfarin sodium,to a 50-mLvolumetric flask,and add 5mLof Internal standard solutionand about 30mLof Solvent mixture.Sonicate for 10minutes,and then shake by mechanical means for 60minutes.Dilute with Solventmixture to volume,and filter.
Procedure Separately inject equal volumes (about 20µL)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 C19H15NaO4in the portion of Tablets taken by the formula:
(330.32/308.34)C(RU/RS),in which 330.32and 308.34are the molecular weights of warfarin sodium and warfarin,respectively;Cis the concentration,in mg per mL,of USP Warfarin RSin the Standard preparation;and RUand RSare the ratios of the peak responses of warfarin to those of propylparaben obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6