A: Infrared Absorption á197Mñ.

B: It responds to the tests for Bismuth á191ñ.

Mobile phase— Prepare a mixture of methanol and 0.06Macetic acid (550:450),filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Diluent— Use a mixture of acetonitrile and water (1:1).

Standard solution— Transfer about 20mg of USP Salicylic Acid RS,accurately weighed,to a 100-mLvolumetric flask,add 20mLof Diluent,and swirl to dissolve.Dilute with Diluentto volume,and mix.Transfer 5.0mLof this stock solution to a 50-mLvolumetric flask,dilute with Diluentto volume,and mix.This Standard solutioncontains about 0.02mg of USP Salicylic Acid RSper mL.

Test solution— Add about 260mg of Bismuth Subsalicylate,accurately weighed,to a glass centrifuge tube,add about 12mLof acetonitrile,shake by mechanical means for 20minutes,and centrifuge.Decant the supernatant into a suitable container.Repeat the acetonitrile addition,shaking,centrifuging,and decanting,combining the decanted liquid with the first decantate.Pass the combined liquid through a filter having a 0.5-µm or finer porosity,collecting the filtrate in a 50-mLvolumetric flask.Wash the container with 5mLof acetonitrile,and filter the wash,collecting the filtrate in the volumetric flask.Dilute with water to volume,and mix.

Chromatographic system— The liquid chromatograph is equipped with a 300-nm detector,a 3.2-mm ×1.5-cm guard column that contains 5-µm packing L1,and a 4.6-mm ×30-cm analytical column that contains 5-µm packing L1.The flow rate is about 1mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20µL)of the Standard solutionand the Test solutioninto the chromatograph,and measure the peak area responses.Calculate the percentage of free salicylic acid in the Bismuth Subsalicylate taken by the formula: in which Cis the concentration,in mg per mL,of USP Salicylic Acid RSin the Standard solution;Wis the weight,in mg,of the Bismuth Subsalicylate taken to prepare the Test solution;and rUand rSare the salicylic acid peak area responses obtained from the Test solutionand the Standard solution,respectively.Not more than 0.2%is found.

Standard solution— Transfer 3.0mLeach of solutions containing 1000µg per mLof copper,lead,and silver,respectively,to a 2000-mLvolumetric flask,dilute with 1Mnitric acid to volume,and mix.[NOTE—The concentrations of copper,lead,and silver may be modified by using different volumes or concentrations to bring the absorption response within the working range of the atomic absorption spectrophotometer.]

Test solution— Ignite about 3g of it,accurately weighed,in a porcelain crucible,cool,and cautiously add 6Mnitric acid to dissolve the residue,and evaporate on a steam bath.Ignite the residue,cool,and transfer the residue to a tared conical flask,wash the flask with about 5mLof 6Mnitric acid,adding the wash to the conical flask.Dissolve the residue with the aid of heat,and add water to obtain a solution weighing 20.0g. [NOTE—The concentrate of Bismuth Subsalicyclate may be modified by using the same proportions used for modifying the Standard solutionby using a different quantity or by further dilution.]

Procedure— Concomitantly determine the absorbances of the Standard solutionand the Test solutionat the emission lines of 324.7nm,217nm,and 328.1nm,for copper,lead,and silver,respectively,with an atomic absorption spectrophotometer (see Spectrophotometry and Light-scattering á851ñ)equipped with copper,lead,and silver hollow-cathode lamps and an oxidizing flame.The absorbances of the Test solutiondo not exceed those of the Standard solutionfor each element (10µg per g).

Standard solution— Transfer 242.0mg of bismuth nitrate pentahydrate to a 100-mLvolumetric flask,add 3mLof 1.5Mnitric acid and swirl to dissolve,dilute with water to volume,and mix.Transfer 1.0mLof this solution to a 500-mLvolumetric flask,add 250mLof 1.5Mnitric acid,dilute with water to volume,and mix.This solution contains 2µg of bismuth (Bi)per mL.[NOTE—The concentration of bismuth in this solution may be modified by using a lesser dilution or by further dilution to bring the absorption response within the working range of the atomic absorption spectrophotometer.]

Test solution— Prepare a mixture of 5.0g of Bismuth Subsalicylate and 100mLof water,and stir the suspension thus obtained for 2hours at 20to 23.Filter through filter paper.Filter the filtrate thus obtained through a filter having a porosity of 0.1µm or less.To 10.0mLof the filtrate add 0.1mLof nitric acid. [NOTE—The concentrate of Bismuth Subsalicyclate may be modified by using the same proportions used for modifying the Standard Solutionby using a different quantity or by further dilution.]

Procedure— Concomitantly determine the absorbances of the Standard solutionand the Test solutionat the emission line of 223.06nm for bismuth with an atomic absorption spectrophotometer (see Spectrophotometry and Light-scattering á851ñ)equipped with a bismuth hollow-cathode lamp and an oxidizing flame.The absorbances of the Test solutiondo not exceed those of the Standard solution(40µg per g).

Ferric ammonium sulfate solution— Transfer 20.0mLof ferric ammonium sulfate TSand 5.0mLof 1Nhydrochloric acid to a 100-mLvolumetric flask,dilute with water to volume,and mix.

Standard stock solution— Prepare a solution of USP Salicylic Acid RSin water having a known concentration of about 0.2mg per mL.

Standard preparation— Transfer 25.0mLof the Standard stock solutionto a beaker,add about 70mLof water,adjust with 0.5Nsodium hydroxide or 1Nhydrochloric acid to a pHof 4.5.Transfer this solution to a 100-mLvolumetric flask with the aid of water,dilute with water to volume,and mix.

Assay preparation— Transfer about 52mg of Bismuth Subsalicylate,previously dried at 105for 3hours and accurately weighed,to a 200-mLvolumetric flask.Add 10mLof 0.5Nsodium hydroxide,heat on a steam bath for 15minutes,allow to cool,dilute with water to volume,and mix.Centrifuge about 70mLof this solution,then transfer 50.0mLof the clear supernatant to a beaker.Add about 40mLof water,and adjust with 0.5Nsodium hydroxide or 1Nhydrochloric acid to a pHof 4.5.Transfer this solution to a 100-mLvolumetric flask with the aid of water,dilute with water to volume,and mix.

Blank— Use water previously adjusted with 0.5Nsodium hydroxide or 1Nhydrochloric acid to a pHof 4.5.

Procedure— To three separate 50-mLconical flasks add 25.0mLof the Standard preparation,the Assay preparation,and the Blank,respectively.To each flask add 1.0mLof Ferric ammonium sulfate solution,and mix to produce the Reacted standard preparation,the Reacted assay preparation,and the Reacted blank solution,respectively.To a second set of three separate 50-mLconical flasks add 25.0mLof the Standard preparation,the Assay preparation,and the Blank,respectively.To each flask add 1.0mLof 0.05Nhydrochloric acid,and mix to produce the Unreacted standard preparation,the Unreacted assay preparation,and the Unreacted blank solution,respectively.Concomitantly determine the absorbances of the six solutions at the wavelength of maximum absorption at about 525nm,using water to zero the spectrophotometer.Calculate the percentage of total salicylates in the portion of Bismuth Subsalicylate taken by the formula: in which Cis the concentration,in mg per mL,of USP Salicylic Acid RSin the Standard stock solution;Wis the weight,in mg,of Bismuth Subsalicylate taken to prepare the Assay preparation;AUris the absorbance of the Reacted assay preparation;AUuis the absorbance of the Unreacted assay preparation;ASris the absorbance of the Reacted standard preparation;ASuis the absorbance of the Unreacted standard preparation;and Bis the difference in the absorption of the Reacted blank solutionand the absorption of the Unreacted blank solution.