A: Transfer the finely ground contents of 1Tablet to a test tube,add 5mLof methanol,shake for 5minutes,and centrifuge.Use the clear supernatant as the Test solution.Prepare a Standard solutionin methanol containing,in each mL,about 65mg of USP Aspirin RSand 20mg of USP Propoxyphene Napsylate RS.Apply 10µLof the Test solutionon a line parallel to and about 2cm from the bottom edge of a 20-×5-cm thin-layer chromatographic plate (see Chromatography á621ñ)coated with chromatographic silica gel mixture,and apply 10µLof the Standard solutionseparately on the starting line.Place the plate in a developing chamber containing a mixture of chloroform,butyl acetate,and formic acid (60:40:20),and develop the chromatogram until the solvent front has moved about 15cm above the line of application.Remove the plate,allow to dry in a hood,and view under short-wavelength UVlight:the solution under test exhibits two principal spots having intensities and RFvalues identical to those of the two principal spots obtained from the Standard solution.

B: The Assay preparationprepared as directed in the Assayis dextrorotatory.

Medium:pH4.5acetate buffer ,prepared as directed in the test for Dissolutionunder Propoxyphene Hydrochloride,Aspirin,and Caffeine Capsules;500mL.

Apparatus 1: 100rpm.

Time: 60minutes.

Determination of dissolved propoxyphene napsylate—

Internal standard solution and pH9.0buffer—Prepare as directed in the test for Dissolutionunder Propoxyphene Hydrochloride,Aspirin,and Caffeine Capsules.

Standard preparation and Procedure—Proceed as directed in the test for Dissolutionunder Propoxyphene Napsylate Tablets.

Determination of dissolved aspirin— Proceed as directed for Determination of dissolved aspirinin the test for Dissolutionunder Propoxyphene Hydrochloride,Aspirin,and Caffeine Capsules.

Tolerances— Not less than 75%(Q)of the labeled amount of C22H29NO2·C10H8O3S·H2Oand not less than 75%(Q)of the labeled amount of C9H8O4are dissolved in 60minutes.

Ferric chloride-urea reagent— Dissolve by swirling,without the aid of heat,60g of urea in a mixture of 8mLof ferric chloride solution (6in 10)and 42mLof 0.05Nhydrochloric acid.Adjust this solution by the addition of 6Nhydrochloric acid to a pHof 3.2,if necessary.

Standard preparation— Transfer 15.0mg of USP Salicylic Acid RS,accurately weighed,to a 100-mLvolumetric flask,add chloroform to volume,and mix.Transfer 10.0mLof this solution to a 100-mLvolumetric flask containing 20mLof methanol,4drops of hydrochloric acid,and 20mLof a 1in 10solution of glacial acetic acid in ether,dilute with chloroform to volume,and mix.

Test preparation— Pack a pledget of glass wool in the base of a 25-×200-mm chromatographic tube.In a beaker,prepare a mixture of 6g of chromatographic siliceous earth,2mLof freshly prepared Ferric chloride-urea reagent,and 40mLof chloroform.Transfer the mixture to the chromatographic tube.Rinse the beaker with 15mLof chloroform,transfer to the column,and pack tightly.Place a small amount of glass wool at the top of the column.Weigh accurately a quantity of the finely powdered contents of Tablets,equivalent to about 50mg of aspirin,mix with 10mLof chloroform by stirring for 3minutes,and transfer with the aid of 10mLof chloroform to the chromatographic column.Pass 40mLof chloroform through the column,rinse the tip of the chromatographic tube with chloroform,and discard the eluate.Prepare as a receiver a 100-mLvolumetric flask containing 20mLof methanol and 4drops of hydrochloric acid,and elute any salicylic acid from the column by passing 20mLof a 1in 10solution of glacial acetic acid in ether that recently has been saturated with water,followed by 30mLof chloroform.Dilute the eluate with chloroform to volume,and mix.

Procedure— Concomitantly determine the absorbances of the Standard preparationand the Test preparationin 1-cm cells at the wavelength of maximum absorbance at about 306nm,with a suitable spectrophotometer,using as the blank a solvent mixture of the same composition as that used for the Standard preparation:the absorbance of the Test preparationdoes not exceed that of the Standard preparation(3.0%,calculated on the basis of the labeled content of aspirin).

Internal standard solution— Dissolve n-tricosane in chloroform to obtain a solution containing about 0.6mg per mL.

Standard preparation— Transfer 50mg of USP Propoxyphene Napsylate RSand 163mg of USP Aspirin RS,all accurately weighed,to a 50-mLvolumetric flask.Add 10mLof acetone,and swirl to dissolve the Reference Standards completely.Dilute with water to volume,and mix.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 100mg of propoxyphene napsylate,to a 100-mLvolumetric flask containing 20mLof acetone,and sonicate for about 1minute.Dilute the milky solution with water to volume,mix,and filter,discarding the first 20mLof the filtrate.

Procedure— Transfer 5.0-mLaliquots of the Assay preparationand the Standard preparationto separate 60-mLseparators.To each add 5.0mLof sodium carbonate solution (1in 5)and 5.0mLof Internal standard solution.Shake vigorously for 5minutes,and allow the layers to separate.Drain the chloroform layer through phase-separating paper,suitably supported in a funnel,into a screw-capped test tube.Extract with one 5-mLportion of chloroform,and drain the chloroform layer through phase-separating paper.Evaporate the combined chloroform extracts,using a stream of dry nitrogen,to a final volume of about 2mL.Inject separately a suitable volume,equivalent to about 6.4µg of propoxyphene,of the chloroform extracts from the Assay preparationand the Standard preparationinto a suitable gas chromatograph equipped with a flame-ionization detector.The column is typically 120cm ×3mm and is packed with 3%phase G3on support S1A.The temperature of the injection port is 200,the column temperature is 175,and the carrier gas is nitrogen flowing at the rate of about 60mLper minute.Relative retention times are 1.0for the internal standard,and 1.7for propoxyphene.In a suitable chromatogram,the resolution factor is not less than 1.0and the relative standard deviation for five replicate injections of the Standard preparationis not more than 2.0.Calculate the quantity,in mg,of C22H29NO2·C10H8O3S·H2Oin the portion of Tablets taken by the formula: in which 565.72and 547.72are the molecular weights of propoxyphene napsylate monohydrate and anhydrous propoxyphene napsylate,respectively,Cis the concentration,in mg per mL,of anhydrous propoxyphene napsylate in the Standard preparation,as determined from the concentration of USP Propoxyphene Napsylate RScorrected for moisture content by a titrimetric water determination,and RUand RSare the peak response ratios obtained from the Assay preparationand the Standard preparation,respectively.

Sodium hydroxide reagent— Dissolve 1g of polyoxyethylene (23)lauryl ether in about 100mLof hot water contained in a 1000-mLvolumetric flask.Dilute with water to about 600mL,and dissolve 10g of sodium hydroxide in this solution.Dilute with water to volume,and mix.

Ferric nitrate reagent— Mix 70mLof nitric acid with about 600mLof water contained in a 1000-mLvolumetric flask.Dissolve 40g of ferric nitrate [Fe(NO3)3·9H2O]in this solution,dilute with water to volume,and mix.

Standard preparation and Assay preparation—Prepare as directed in the Assay for propoxyphene napsylate.

Procedure— Into separate 25-mLvolumetric flasks pipet 2mLeach of the Standard preparationand the Assay preparation,and 2mLof dilute acetone (2in 10)to provide the blank.Into each flask pipet 5mLof Sodium hydroxide reagent,mix by gentle swirling,and allow to stand at room temperature for 8minutes.Dilute with Ferric nitrate reagentto volume,and mix.Concomitantly determine the absorbances of both solutions against the blank in 1-cm cells at the wavelength of maximum absorbance at about 530nm,taking care to allow the solutions to reach an equilibrium temperature in the cell compartment.The color intensity is temperature-dependent.Calculate the quantity,in mg,of C9H8O4in the portion taken for the Assay preparationby the formula: in which Cis the concentration,in mg per mL,of USP Aspirin RSin the Standard preparation,and AUand ASare the absorbances of the solutions from the Assay preparationand Standard preparation,respectively.