Acetaminophen and Aspirin Tablets

» Acetaminophen and Aspirin Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of acetaminophen (C8H9NO2) and aspirin (C9H8O4).

Packaging and storage— Preserve in tight containers, and store at controlled room temperature.

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USP Acetaminophen RS

USP Aspirin RS

USP Salicylic Acid RS

Identification— The relative retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.

Dissolution, Procedure for a Pooled Sample

711

—

Medium: water; 900 mL.

Apparatus 2: 50 rpm.

Time: 45 minutes.

Mobile phase— Prepare as directed under Assay.

Solvent mixture— Prepare as directed under Assay.

Internal standard solution— Prepare a solution of benzoic acid in methanol having a concentration of about 1 mg per mL.

Standard preparation I— Dissolve an accurately weighed quantity of USP Salicylic Acid RS in the Solvent mixture to obtain a solution having a known concentration of about 70 µg per mL. Combine 4.0 mL of this solution and 1.0 mL of the Internal standard solution, and mix.

Standard preparation II— Dissolve accurately weighed quantities of USP Acetaminophen RS and USP Aspirin RS in the Solvent mixture to obtain a solution having known concentrations of about 360 µg of acetaminophen and about 360 µg of aspirin per mL. Combine 4.0 mL of this solution and 1.0 mL of the Internal standard solution, and mix.

Test preparation— Combine 4.0 mL of a filtered portion of the solution under test and 1.0 mL of the Internal standard solution, and mix.

Chromatographic system— Proceed as directed under Assay.

Procedure— Separately inject equal volumes (about 20 µL) of the two Standard preparations and the Test preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.3 for acetaminophen, 0.4 for salicylic acid, 0.6 for aspirin, and 1.0 for benzoic acid. Determine the amount of acetaminophen (C8H9NO2) dissolved by the formula:

90(C/W)(RU / RS)

in which C is the concentration, in µg per mL, of USP Acetaminophen RS in Standard preparation II; RU and RS are the relative peak response ratios obtained from the Test preparation and Standard preparation II, respectively; and W is the labeled amount, in mg, of acetaminophen. Determine the amount of aspirin (C9H8O4) dissolved by the formula:

{[90C1(RU1 / RS1)] + [90C2(RU2 / RS2)(1.3044)]} / W

in which C1 and C2 are the concentrations, in µg per mL, of USP Aspirin RS in Standard preparation II and USP Salicylic Acid RS in Standard preparation I, respectively; RU1 and RS1 are the relative peak response ratios for the aspirin peak and the internal standard peak obtained from the Test preparation and Standard preparation II, respectively; RU2 and RS2 are the relative peak response ratios for the salicylic acid peak and the internal standard peak obtained from the Test preparation and Standard preparation I, respectively; and W is the labeled amount, in mg, of aspirin.

Tolerances— Not less than 75% (Q) of the labeled amounts of C8H9NO2 and C9H8O4 is dissolved in 45 minutes.

Uniformity of dosage units

905

: meet the requirements for Content Uniformity with respect to acetaminophen and to aspirin.

Limit of salicylic acid—

Solvent mixture, Mobile phase, Internal standard solution, and Chromatographic system— Prepare as directed in the Assay.

Procedure— Dissolve a suitable quantity of USP Salicylic Acid RS, accurately weighed, in Solvent mixture to obtain a solution having a known concentration of about 1.0 mg per mL. Transfer 1.0-mL, 5.0-mL, and 10.0-mL portions, respectively, of this solution to separate 100-mL volumetric flasks, add 10.0 mL of Internal standard solution to each flask, dilute with Solvent mixture to volume, and mix. Chromatograph these three Standard solutions as directed in the Assay. Plot the ratios of the peak responses for salicylic acid and benzoic acid for each of the Standard solutions versus concentrations, in mg per mL, of salicylic acid, and draw the straight line best fitting the three plotted points. From the graph so obtained, and from the ratio of the peak responses for salicylic acid and benzoic acid in the chromatogram of the Assay preparation as obtained in the Assay, determine the concentration, in mg per mL, of salicylic acid (C7H6O3) in the Assay preparation, and calculate the percentage of salicylic acid in relation to the concentration of aspirin in the Assay preparation, as determined in the Assay. Not more than 3.0% is found.

Assay— [note—Use clean, dry glassware. Inject the Standard preparation and the Assay preparation promptly after preparation. ]

Solvent mixture— Prepare a mixture of chloroform, methanol, and glacial acetic acid (78:20:2).

Mobile phase— Transfer 225 mg of tetramethylammonium hydroxide pentahydrate to a 1000-mL flask, and add 750 mL of water, 125 mL of methanol, 125 mL of acetonitrile, and 1.0 mL of glacial acetic acid. Stir for 3 minutes, pass through a membrane filter having a 0.5-µm or finer porosity, and degas.

Internal standard solution— Dissolve benzoic acid in Solvent mixture to obtain a solution having a concentration of about 20 mg per mL.

Standard preparation— Transfer about 325 mg of USP Acetaminophen RS and about 325 mg of USP Aspirin RS, each accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of Internal standard solution, dilute with Solvent mixture to volume, and mix.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 325 mg of acetaminophen, to a 100-mL volumetric flask, add 10.0 mL of Internal standard solution and about 50 mL of Solvent mixture, and sonicate for about 3 minutes. Dilute with Solvent mixture to volume, and mix. Pass a portion of this solution through a filter having a 2.5-µm or finer porosity, and use the filtrate as the Assay preparation.

Chromatographic system— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph four replicate injections of the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for either analyte is not more than 3.0%.

Procedure— Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The retention times are about 2, 3, 5, and 8 minutes for acetaminophen, salicylic acid (if present), aspirin, and benzoic acid, respectively. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in the portion of Tablets taken by the formula:

100C(RU / RS)

in which C is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; and RU and RS are the ratios of the peak responses of acetaminophen and benzoic acid obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of aspirin (C9H8O4) in the portion of Tablets taken by the same formula, except to read “USP Aspirin RS” where “USP Acetaminophen RS” is specified, and “aspirin” where “acetaminophen” is specified.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Clydewyn M. Anthony, Ph.D. Senior Scientific Liaison 1-301-816-8139	(SM22010) Monographs - Small Molecules 2
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 2034

Pharmacopeial Forum: Volume No. 30(1) Page 41