Test specimen— To about 50mLof water add a quantity of finely powdered Tablets,equivalent to about 800mg of mesalamine.Boil the mixture for about 5minutes,with constant stirring.Filter the hot solution,and allow the filtrate to cool.Collect the precipitated crystals,and dry at about 110.

pH6.0Phosphate buffer— Transfer about 43.35g of monobasic potassium phosphate and 1.65g of sodium hydroxide to a 2-liter volumetric flask.Dissolve in and dilute with water to volume,and mix.Adjust with 1Nsodium hydroxide or phosphoric acid to a pHof 6.0,and mix.

Sodium hydroxide solution— Transfer 133.6g of sodium hydroxide to a 2-liter volumetric flask,dissolve in and dilute with water to volume,and mix.

Media: 0.1Nhydrochloric acid,500mLfor Acid stage;pH6.0Phosphate buffer,900mLfor Buffer stages.

Apparatus 2: 100rpm for Acid stageand for Buffer stage 1;50rpm for Buffer stage 2.

Times: 2hours for Acid stage;1hour for Buffer stage 1;90minutes for Buffer stage 2.

ACID STAGE— After 2hours of operation,withdraw an aliquot of the fluid,discard the remaining solution,and retain the Tablets in proper order,so that each will be returned to its respective vessel later on.Blot the Tablets with a paper towel to dry,and proceed immediately as directed for Buffer stage 1.

BUFFER STAGE1— [NOTE—Use buffer that has been equilibrated to a temperature of 37±0.5.]Transfer pH6.0Phosphate bufferto each of the dissolution vessels,and place each Tablet from the Acid stageinto its respective vessel.After 1hour remove a 50-mLaliquot,and proceed immediately as directed for Buffer stage 2.

BUFFER STAGE2— Add 50mLof Sodium hydroxide solutionto each dissolution vessel to adjust to a pHof 7.2,and continue the run.

Mobile phase— Proceed as directed in the Assay.

Chromatographic system— Proceed as directed in the Assay.To evaluate the system suitability requirements,use the System suitability preparation,Standard stock preparation,and the Standard preparationprepared as directed in the Assay.

Test solution— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 400mg of mesalamine,to a 500-mLvolumetric flask.Add 50mLof 1Nhydrochloric acid,and sonicate to dissolve.Shake by mechanical means for 10minutes,dilute with water to volume,mix,and pass through a filter having a 0.5-µm or finer porosity.[NOTE—Use an aliquot of this solution for the Assay preparation.]

Procedure— Inject a volume (about 20µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the areas for all the peaks.Calculate the percentage of each impurity in the portion of Tablets taken by the formula: in which riis the peak response for each impurity;and rsis the sum of the responses of all the peaks:the largest secondary peak is not more than 1.0%of the total area;not more than 0.5%of any other individual impurity is found;and not more than 2.0%of total impurities is found.

Mobile phase— Dissolve 4.3g of sodium 1-octanesulfonate in 1liter of water.Adjust with phosphoric acid to a pHof 2.15,pass through a filter having a 0.45-µm or finer porosity,and degas.

System suitability preparation— Transfer about 20mg each of 3-aminosalicylic acid and USP Salicylic Acid RS,accurately weighed,to a 200-mLvolumetric flask.Dissolve in 50mLof 1Nhydrochloric acid,sonicating to dissolve,dilute with water to volume,and mix.Dilute the solution so obtained quantitatively and stepwise with water,and mix to obtain a solution having known concentrations of about 0.01mg each of 3-aminosalicylic acid and salicylic acid per mL.

Standard stock preparation— Transfer about 25mg of USP Mesalamine RS,accurately weighed,to a 25-mLvolumetric flask.Dissolve in 5mLof 0.25Nhydrochloric acid,sonicating to dissolve,dilute with water to volume,and mix.

Standard preparation— Transfer 10.0mLof Standard stock preparationand 5.0mLof System suitability preparationto a 50-mLvolumetric flask.Dilute with water to volume,mix,and pass through a filter having a 0.5-µm or finer porosity.

Assay preparation— Pipet a 25.0-mLaliquot of the Test solution,obtained as directed for the Chromatographic puritytest,into a 100-mLvolumetric flask,dilute with water to volume,mix,and pass through a filter having a 0.5-µm or finer porosity.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 230-nm detector,a 4.6-mm ×3.3-cm analytical column that contains 3-µm base-deactivated packing L1,and two 4.6-mm ×3.0-cm precolumns,each containing 10-µm packing L1and being located between the pump and the injector.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between mesalamine and salicylic acid or 3-aminosalicylic acid is not less than 2;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 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 mesalamine (C7H7NO3)in the portion of Tablets taken by the formula: in which Cis the concentration,in mg per mL,of USP Mesalamine RSin the Standard preparation;and rUand rSare the mesalamine peak responses obtained from the Assay preparationand the Standard preparation,respectively.