Printed on: Fri Jan 05 2024, 10:30:57 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-BB9579E0-110B-4D39-9A9E-5E5BCDF0CE95_1_en-US

Printed by: USP NF Official Date: Official as of 01-Dec-2017 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: p4y31 DOI: https://doi.org/10.31003/USPNF_M230_01_01
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Acceptance criteria: 90.0%–110.0% of the labeled amount

Acetaminophen and Aspirin Tablets of acetaminophen (C8H9NO2) and aspirin (C9H8O4)
DEFINITION PERFORMANCE TESTS
Acetaminophen and Aspirin Tablets contain NLT 90.0% and • DISSOLUTION á711ñ
NMT 110.0% of the labeled amount of acetaminophen Procedure for a pooled sample
(C8H9NO2) and aspirin (C9H8O4). Medium: Water; 900 mL
IDENTIFICATION Apparatus 2: 50 rpm
• A. The retention times of the major peaks of the Sample Time: 45 min
solution correspond to those of the Standard solution, as Solution A, Mobile phase, and Chromatographic system
obtained in the Assay. (except for Injection volume): Proceed as directed in the
Assay.
ASSAY Injection volume: 20 µL
• PROCEDURE Internal standard solution: 1 mg/mL of benzoic acid in
[NOTE—Use clean and dry glassware. Inject the methanol
Standard solution and the Sample solution promptly Standard stock solution A: 70 µg/mL of USP Salicylic
after preparation.] Acid RS in Solution A
Solution A: Chloroform, methanol, and glacial acetic acid Standard solution A: Combine 4.0 mL of Standard stock
(78:20:2) solution A and 1.0 mL of Internal standard solution.
Mobile phase: Transfer 225 mg of tetramethylammonium Standard stock solution B: 360 µg/mL each of USP
hydroxide pentahydrate to a 1000-mL flask. Add 750 mL of Acetaminophen RS and USP Aspirin RS in Solution A
water, 125 mL of methanol, 125 mL of acetonitrile, and Standard solution B: Combine 4.0 mL of Standard stock
1.0 mL of glacial acetic acid. Stir for 3 min, and pass solution B and 1.0 mL of Internal standard solution.

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through a membrane filter of 0.5-µm or finer pore size. Sample stock solution: Filtered portions of sample
Internal standard solution: 20 mg/mL of benzoic acid in suitably diluted with Medium to a concentration that is
Solution A similar to that of Standard stock solution A or Standard stock
Standard solution: 3.25 mg/mL each of USP solution B
Acetaminophen RS and USP Aspirin RS, and 2.0 mg/mL of Sample solution: Combine 4.0 mL of the Sample stock

Sample solution: Nominally 3.25 mg/mL of

acetaminophen in Solution A, prepared as follows. Transfer
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benzoic acid, from Internal standard solution, in Solution A solution and 1.0 mL of Internal standard solution.
Analysis
Samples: Standard solution A, Standard solution B, and
an equivalent of 325 mg of acetaminophen, from NLT 20 Sample solution
finely powdered Tablets, to a 100-mL volumetric flask. Add [NOTE—The relative retention times for
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10.0 mL of Internal standard solution and 50 mL of Solution acetaminophen, salicylic acid, aspirin, and benzoic
A, and sonicate for 3 min. Dilute with Solution A to volume. acid are about 0.3, 0.4, 0.6, and 1.0, respectively.]
Pass a portion of this solution through a filter of 2.5-µm or Calculate the percentage of the labeled amount of
finer pore size. Use the filtrate. acetaminophen (C8H9NO2) dissolved:
Chromatographic system
(See Chromatography á621ñ, System Suitability.) Result = (RU/RS) × (C/W) × 90
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Mode: LC
Detector: UV 280 nm RU = relative peak response ratio of acetaminophen to
Column: 3.9-mm × 30-cm; packing L1 the internal standard from the Sample solution
Flow rate: 2 mL/min RS = relative peak response ratio of acetaminophen to
Injection volume: 5 µL the internal standard from Standard solution B
System suitability C = concentration of USP Acetaminophen RS in
Sample: Standard solution Standard solution B (µg/mL)
[NOTE—The retention times for acetaminophen, W = labeled amount of acetaminophen (mg)
salicylic acid (if present), aspirin, and benzoic acid are
about 2, 3, 5, and 8 min, respectively.] Calculate the percentage of the labeled amount of aspirin
Suitability requirements (C9H8O4) dissolved:
Relative standard deviation: NMT 3.0% for
acetaminophen or aspirin for four replicate injections Result = {[90C1 × (RU1/RS1)] + [90C2 × (RU2/RS2) × 1.3044]}
Analysis /W
Samples: Standard solution and Sample solution
Calculate individually the percentage of the labeled amount C1 = concentration of USP Aspirin RS in Standard
of acetaminophen (C8H9NO2) and aspirin (C9H8O4) in the solution B (µg/mL)
portion of Tablets taken: RU1 = relative peak response ratio of aspirin to the
internal standard from the Sample solution
Result = (RU/RS) × (CS/CU) × 100 RS1 = relative peak response ratio of aspirin to the
internal standard from Standard solution B
RU = peak response ratio of acetaminophen or aspirin C2 = concentration of USP Salicylic Acid RS in Standard
to benzoic acid from the Sample solution solution A (µg/mL)
RS = peak response ratio of acetaminophen or aspirin RU2 = relative peak response ratio of salicylic acid to the
to benzoic acid from the Standard solution internal standard from the Sample solution
CS = concentration of USP Acetaminophen RS or USP RS2 = relative peak response ratio of salicylic acid to the
Aspirin RS in the Standard solution (mg/mL) internal standard from Standard solution A
CU = nominal concentration of acetaminophen or W = labeled amount of aspirin (mg)
aspirin in the Sample solution (mg/mL)

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Printed on: Fri Jan 05 2024, 10:30:57 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-BB9579E0-110B-4D39-9A9E-5E5BCDF0CE95_1_en-US
Printed by: USP NF Official Date: Official as of 01-Dec-2017 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: p4y31 DOI: https://doi.org/10.31003/USPNF_M230_01_01
2

Tolerances: NLT 75% (Q) of the labeled amount of concentrations, in mg/mL, of salicylic acid, and draw the
acetaminophen (C8H9NO2) and aspirin (C9H8O4) is straight line best fitting the three plotted points. From
dissolved. the graph so obtained, and from the ratio of the peak
• UNIFORMITY OF DOSAGE UNITS á905ñ, Content Uniformity: responses for salicylic acid and benzoic acid from the
Meet the requirements with respect to acetaminophen and Sample solution as obtained in the Assay, determine the
to aspirin concentration, in mg/mL, of salicylic acid (C7H6O3) in the
Sample solution.
IMPURITIES Calculate the percentage of salicylic acid in relation to the
• LIMIT OF SALICYLIC ACID concentration of aspirin in the Sample solution, as
Solution A, Mobile phase, Internal standard solution, obtained in the Assay.
Sample solution, Chromatographic system, and System Acceptance criteria: NMT 3.0%
suitability: Proceed as directed in the Assay. • 4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG
Standard stock solution: 1.0 mg/mL of USP Salicylic PRODUCTS á227ñ: Meet the requirements
Acid RS in Solution A
Standard solutions: Transfer 1.0-, 5.0-, and 10.0-mL ADDITIONAL REQUIREMENTS
portions of Standard stock solution to separate 100-mL • PACKAGING AND STORAGE: Preserve in tight containers, and
volumetric flasks. Add 10.0 mL of Internal standard solution store at controlled room temperature.
to each flask, and dilute with Solution A to volume. • USP REFERENCE STANDARDS á11ñ
Analysis USP Acetaminophen RS
Samples: Sample solution and Standard solutions USP Aspirin RS
Plot the ratios of the peak responses for salicylic acid and USP Salicylic Acid RS
benzoic acid for each of the Standard solutions versus

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