A: Tablets respond to the Identification tests 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 2 mL of water and 2 drops of methyl red TS to each tube, and shake for about 15 seconds: the solution from the aspirin-containing layer is red, and the solution from the buffer-containing layer is yellow.

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

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

Time: 45 minutes.

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

pH 4.3 Buffer detergent— Dissolve 12.9 g of citric acid monohydrate and 20.6 g of dibasic sodium phosphate heptahydrate in water to make 1000 mL of solution. Add 0.5 mL of a 30% solution of polyoxyethylene (23) lauryl ether, and mix.

Standard preparation— Dissolve a suitable quantity of USP Aspirin RS, accurately weighed, in Medium to obtain a solution having a known concentration of about 0.45 mg 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 16. With the sample line pumping pH 4.3 Buffer detergent, the other lines pumping their respective reagents, the fluorometer set at an excitation wavelength of 298 nm and an emission wavelength of 425 nm, adjust the system until a steady fluorescence baseline has been achieved. Start the sampler, and conduct determinations at a rate of 40 per hour, using a ratio of about 5:1 for sample and wash time. Record the fluorescence values of the Standard preparation and the solution under test. Calculate the quantity, in mg, of aspirin (C9H8O4) dissolved by the formula: in which C is the concentration, in mg per mL, of USP Aspirin RS in the Standard preparation; and FU and FS are 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 45 minutes.

(Official January 1, 2007)

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 Suitability under Chromatography 621).

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

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

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

Resolution solution— Transfer 5.0 mL of the stock solution used to prepare the Standard aspirin preparation to a 100-mL volumetric flask, add 5.0 mL of 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 2500 mg of aspirin, to a 120-mL blender jar containing 100.0 mL of Solvent mixture, and blend at high speed for about 1.5 minutes. Immediately filter a portion of the mixture thus obtained, and transfer 1.0 mL of the filtrate to a 100-mL volumetric 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 621)—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 3.5 mL per 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 10 µL) of the Standard aspirin preparation, the Standard salicylic acid preparation, and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.7 for aspirin and 1.0 for salicylic acid. Calculate the quantity, in mg, of aspirin (C9H8O4) in each Tablet taken by the formula: in which C is the concentration, in mg per mL, of USP Aspirin RS in the Standard aspirin preparation; N is the number of Tablets taken to prepare the Assay preparation; and rU and rS are the aspirin peak responses obtained from the Assay preparation and the Standard preparation, respectively. Calculate the percentage of free salicylic acid in the Tablets taken by the formula: in which C is the concentration, in µg per mL, of USP Salicylic Acid RS in the Standard salicylic acid preparation; a is the quantity, in mg, of aspirin in the number of Tablets taken to prepare the Assay preparation, based on the labeled amount; and rU and rS are the salicylic acid peak responses obtained from the Assay preparation and the Standard salicylic acid preparation, respectively: not more than 3.0% is found.

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

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

Procedure— Pipet 20 mL of the Assay preparation into a 250-mL beaker, add 20 mL of water, then add, in the order named and with continuous stirring, 25.0 mL of 0.05 M Edetate disodium titrant and 20 mL of acetic acid-ammonium acetate buffer TS, and heat the solution near the boiling temperature for 5 minutes. Cool, add 50 mL of alcohol and 2 mL of dithizone TS, and mix. Titrate with 0.05 M zinc sulfate VS until the color changes from green-violet to rose-pink. Perform a blank determination, substituting 10 mL of water for the Assay preparation, and make any necessary corrections. Each mL of 0.05 to 3.900 mg 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 40 mg of magnesium oxide, into a 400-mL beaker, and add, with mixing, 20 mL of triethanolamine and 200 mL of water. Cool the solution for 10 minutes, while stirring, by immersion of the beaker in an ice bath. Remove the beaker from the ice bath, and add 15 mL of ammonia–ammonium chloride buffer TS and 2 drops of eriochrome black indicator solution (prepared by dissolving 200 mg of eriochrome black T in a mixture of 15 mL of triethanolamine and 5 mL of dehydrated alcohol, and mixing). Titrate with 0.05 M edetate disodium VS to a blue endpoint, allowing about 60 seconds between drops of titrant as the endpoint is approached (after first color change is observed). [NOTE—The titration should be completed within 10 minutes 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 preparation used, and make any necessary correction. Each mL of 0.05 M edetate disodium consumed is equivalent to 2.015 mg of MgO.