A: Tablets respond to the Identificationtests under Aspirin,Alumina,and Magnesia Tablets.

B: Where the Tablets are composed of two layers,scrape a small amount of each layer into separate test tubes.Add 2mLof water and 2drops of methyl red TSto each tube,and shake for about 15seconds:the solution from the aspirin-containing layer is red,and the solution from the buffer-containing layer is yellow.

Medium: 0.05Macetate buffer,prepared by mixing 2.99g of sodium acetate (trihydrate)and 1.66mLof glacial acetic acid with water to obtain 1000mLof solution having a pHof 4.50±0.05;900mL.

Apparatus 1 (10-mesh screen):100rpm.

Time: 45minutes.

Alkaline detergent solution— Prepare a suitable mixture of 1Nsodium hydroxide and a 30%solution of polyoxyethylene (23)lauryl ether (1000:0.5).

pH4.3Buffer detergent— Dissolve 12.9g of citric acid monohydrate and 20.6g of dibasic sodium phosphate heptahydrate in water to make 1000mLof solution.Add 0.5mLof a 30%solution of polyoxyethylene (23)lauryl ether,and mix.

Standard preparation— Dissolve a suitable quantity of USP Aspirin RS,accurately weighed,in Mediumto obtain a solution having a known concentration of about 0.45mg per mL.

Procedure— Use an automatic analyzer consisting of (1)a liquid sampler;(2)a proportioning pump;(3)a suitable fluorometer equipped with a 0.4-cm flow cell and suitable recording devices;and (4)a manifold consisting of the components illustrated in the diagram in the chapter Automated Methods of Analysis á16ñ.With the sample line pumping pH4.3Buffer detergent,the other lines pumping their respective reagents,the fluorometer set at an excitation wavelength of 298nm and an emission wavelength of 425nm,adjust the system until a steady fluorescence baseline has been achieved.Start the sampler,and conduct determinations at a rate of 40per hour,using a ratio of about 5:1for sample and wash time.Record the fluorescence values of the Standard preparationand the solution under test.Calculate the quantity,in mg,of aspirin (C9H8O4)dissolved by the formula: in which Cis the concentration,in mg per mL,of USP Aspirin RSin the Standard preparation;and FUand FSare the fluorescence values of the solution under test and the Standard preparation,respectively.

Tolerances— Not less than 75%(Q)of the labeled amount of aspirin (C9H8O4)is dissolved in 45minutes.

Mobile phase— Prepare a suitable mixture of water,methanol,and phosphoric acid (700:300:30).Filter and degas before use.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Solvent mixture— Mix 20mLof hydrochloric acid and 2000mLof dehydrated alcohol.

Standard aspirin preparation— Dissolve a suitable quantity of USP Aspirin RS,accurately weighed,by blending in a 120-mLblender jar at high speed for about 1.5minutes with an accurately measured volume of Solvent mixtureto obtain a stock solution having a known concentration of about 5mg per mL.Immediately transfer 5.0mLof this stock solution to a 100-mLvolumetric flask,dilute with dehydrated alcohol to volume,and mix.This solution contains about 0.25mg per mL.[NOTE—Use these solutions within 1hour.]

Standard salicylic acid preparation— Dissolve a suitable quantity of USP Salicylic Acid RSin dehydrated alcohol to obtain a stock solution having a known concentration of about 5mg per mL.Transfer 3.0mLof this stock solution to a 100-mLvolumetric flask,dilute with Solvent mixtureto volume,and mix.Transfer 5.0mLof this intermediate stock solution to a second 100-mLvolumetric flask,dilute with dehydrated alcohol to volume,and mix.This solution contains about 7.5µg per mL.

Resolution solution— Transfer 5.0mLof the stock solution used to prepare the Standard aspirin preparationto a 100-mLvolumetric flask,add 5.0mLof the intermediate stock solution used to prepare the Standard salicylic acid preparation,dilute with dehydrated alcohol to volume,and mix.

Assay preparation— Transfer an accurately counted number of Tablets,equivalent to about 2500mg of aspirin,to a 120-mLblender jar containing 100.0mLof Solvent mixture,and blend at high speed for about 1.5minutes.Immediately filter a portion of the mixture thus obtained,and transfer 1.0mLof the filtrate to a 100-mLvolumetric flask.Immediately dilute with dehydrated alcohol to volume,and mix.[NOTE—Promptly inject this Assay preparation into the chromatograph as directed for Procedure.]

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 205-nm detector and a 4.6-mm ×3-cm column that contains 5-µm packing L7.The flow rate is about 3.5mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the resolution,R,between the aspirin peak and the salicylic acid peak is not less than 2.Chromatograph the Standard aspirin preparation,and record the responses as directed for Procedure:the tailing factor is not more than 2,and the relative standard deviation for replicate injections is not more than 2.0%.Chromatograph the Standard salicylic acid preparation,and record the responses as directed for Procedure:the tailing factor is not more than 2,and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard aspirin preparation,the Standard salicylic acid preparation,and the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.7for aspirin and 1.0for salicylic acid.Calculate the quantity,in mg,of aspirin (C9H8O4)in each Tablet taken by the formula: in which Cis the concentration,in mg per mL,of USP Aspirin RSin the Standard aspirin preparation;Nis the number of Tablets taken to prepare the Assay preparation;and rUand rSare the aspirin peak responses obtained from the Assay preparationand the Standard preparation,respectively.Calculate the percentage of free salicylic acid in the Tablets taken by the formula: in which Cis the concentration,in µg per mL,of USP Salicylic Acid RSin the Standard salicylic acid preparation;ais the quantity,in mg,of aspirin in the number of Tablets taken to prepare the Assay preparation,based on the labeled amount;and rUand rSare the salicylic acid peak responses obtained from the Assay preparationand the Standard salicylic acid preparation,respectively:not more than 3.0%is found.

Edetate disodium titrant— Prepare and standardize as directed in the Assayunder Ammonium Alum.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 600mg of aluminum hydroxide,to a 150-mLbeaker,add 20mLof water,stir,and slowly add 30mLof 3Nhydrochloric acid.Heat gently,if necessary,to aid solution,cool,and transfer to a 200-mLvolumetric flask.Wash the beaker with water,adding the washings to the flask,add water to volume,and mix.

Procedure— Pipet 20mLof the Assay preparationinto a 250-mLbeaker,add 20mLof water,then add,in the order named and with continuous stirring,25.0mLof 0.05MEdetate disodium titrantand 20mLof acetic acid-ammonium acetate buffer TS,and heat the solution near the boiling temperature for 5minutes.Cool,add 50mLof alcohol and 2mLof dithizone TS,and mix.Titrate with 0.05Mzinc sulfate VSuntil the color changes from green-violet to rose-pink.Perform a blank determination,substituting 10mLof water for the Assay preparation,and make any necessary corrections.Each mLof 0.05to 3.900mg of Al(OH)3.

Assay preparation— Prepare as directed in the Assay for aluminum hydroxide.

Procedure— Pipet a volume of Assay preparation,equivalent to about 40mg of magnesium oxide,into a 400-mLbeaker,and add,with mixing,20mLof triethanolamine and 200mLof water.Cool the solution for 10minutes,while stirring,by immersion of the beaker in an ice bath.Remove the beaker from the ice bath,and add 15mLof ammonia–ammonium chloride buffer TSand 2drops of eriochrome black indicator solution (prepared by dissolving 200mg of eriochrome black Tin a mixture of 15mLof triethanolamine and 5mLof dehydrated alcohol,and mixing).Titrate with 0.05Medetate disodium VSto a blue endpoint,allowing about 60seconds between drops of titrant as the endpoint is approached (after first color change is observed).[NOTE—The titration should be completed within 10minutes after the addition of the buffer and indicator.If any precipitate is observed prior to titration,the solution should be discarded and a new solution prepared.]Perform a blank determination,substituting for the Assay preparation,a volume of water equivalent to the volume of Assay preparationused,and make any necessary correction.Each mLof 0.05Medetate disodium consumed is equivalent to 2.015mg of MgO.