Printed on: Thu Mar 30 2023, 09:48:36 AM(EST) Status: Currently Official on 30-Mar-2023 DocId: GUID-33AD0880-7404-4169-BDD5-F74D808EE77F_5_en-US

Printed by: MICHEL NTAMBWE Official Date: Official as of 01-Jan-2023 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: h2802 DOI: https://doi.org/10.31003/USPNF_M150_05_01
1

Suitability requirements
Acetaminophen Tailing factor: NMT 2.0
Relative standard deviation: NMT ▲0.73%▲ (IRA 1-Jan-2023)
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of acetaminophen (C8H9NO2) in
the portion of Acetaminophen taken:

Result = (rU/rS) × (CS/CU) × 100

rU = peak response ▲of acetaminophen▲ (IRA 1-Jan-2023)

C8H9NO2 151.16 from the Sample solution
Acetamide, N-(4-hydroxyphenyl)-; rS = peak response ▲of acetaminophen▲ (IRA 1-Jan-2023)
4′-Hydroxyacetanilide CAS RN®: 103-90-2; UNII: from the Standard solution
362O9ITL9D. CS = concentration of USP Acetaminophen RS in the
Standard solution (mg/mL)
DEFINITION CU = concentration of Acetaminophen in the Sample
Acetaminophen contains NLT 98.0% and NMT 102.0% of solution (mg/mL)
acetaminophen (C8H9NO2), calculated on the dried basis.
IDENTIFICATION Acceptance criteria: 98.0%–102.0% on the dried basis
• A. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared IMPURITIES
Spectroscopy: 197K • RESIDUE ON IGNITION á281ñ: NMT 0.1%

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• B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as Change to read:
obtained in the Assay.
• LIMIT OF FREE 4-AMINOPHENOL
ASSAY ci Solution A, Solution B, and Mobile phase▲▲ (IRA 1-Jan-2023):
Change to read: Prepare as directed in the Assay.
Standard solution: 1.25 µg/mL of USP 4-Aminophenol RS
• PROCEDURE in methanol
Use low-actinic glassware for preparation of the ▲solutions Sample solution: 25 mg/mL of Acetaminophen in
containing acetaminophen.▲ (IRA 1-Jan-2023) methanol
Solution A: 1.7 g/L of monobasic potassium phosphate and
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▲
Chromatographic system
1.8 g/L of sodium phosphate, dibasic, anhydrous (See Chromatography á621ñ, System Suitability.)
Solution B: Methanol Mode: LC
Mobile phase: See Table 1. Detector: UV 230 nm
Column: 4.6-mm × 10-cm; 3.5-µm packing L7
Table 1 Column temperature: 35°
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Time Solution A Solution B Flow rate: 1 mL/min

(min) (%) (%) Injection volume: 5 µL▲ (IRA 1-Jan-2023)
0 99 1
System suitability
Sample: Standard solution
3 99 1 [NOTE—The relative retention times for 4-aminophenol
7 19 81
and acetaminophen are 0.6 and 1.0, respectively.]
Suitability requirements
7.1 99 1 Relative standard deviation: NMT 5.0%
10 99 1 Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of 4-aminophenol in the portion
Standard ▲stock▲ (IRA 1-Jan-2023) solution: 0.1 mg/mL of USP of Acetaminophen taken:
Acetaminophen RS in methanol
▲
Standard solution: 0.02 mg/mL of USP Acetaminophen Result = (rU/rS) × (CS/CU) × 100
RS from the Standard stock solution in Solution
A▲ (IRA 1-Jan-2023) rU = peak response of 4-aminophenol from the
Sample ▲stock▲ (IRA 1-Jan-2023) solution: 0.1 mg/mL of Sample solution
Acetaminophen in methanol rS = peak response ▲of 4-aminophenol▲ (IRA 1-Jan-2023)
▲
Sample solution: 0.02 mg/mL of Acetaminophen from from the Standard solution
the Sample stock solution in Solution A▲ (IRA 1-Jan-2023) CS = concentration of USP 4-Aminophenol RS in the
Chromatographic system Standard solution (µg/mL)
(See Chromatography á621ñ, System Suitability.) CU = concentration of Acetaminophen in the Sample
Mode: LC solution (µg/mL)
Detector: UV 230 nm
Column: 4.6-mm × 10-cm; 3.5-µm packing L7 Acceptance criteria: NMT 0.005%
Column temperature: 35°
Flow rate: ▲1▲ (IRA 1-Jan-2023) mL/min Change to read:
Injection volume: ▲25▲ (IRA 1-Jan-2023) µL
System suitability • ORGANIC IMPURITIES
Sample: Standard solution Solution A: Methanol, glacial acetic acid, and water
(50:1:950)

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Printed by: MICHEL NTAMBWE Official Date: Official as of 01-Jan-2023 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: h2802 DOI: https://doi.org/10.31003/USPNF_M150_05_01
2

Solution B: Methanol, glacial acetic acid, and water Analysis

(500:1:500) Samples: Standard solution and Sample solution
Mobile phase: See Table 2. Calculate the percentage of ▲acetaminophen related
compound D and▲ (IRA 1-Jan-2023) acetaminophen related
Table 2 compound J in the portion of Acetaminophen taken:
Time Solution A Solution B
(min) (%) (%) Result = (rU/rS) × (CS/CU) × 100
0 82 18
rU = peak response of ▲acetaminophen related
8 82 18 compound D or▲ (IRA 1-Jan-2023) acetaminophen
related compound J from the Sample solution
53 0 100
rS = peak response of ▲acetaminophen related
58 0 100 compound D or▲ (IRA 1-Jan-2023) acetaminophen
59 82 18
related compound J from the Standard solution
CS = concentration of ▲USP Acetaminophen Related
73 82 18 Compound D RS or▲ (IRA 1-Jan-2023) USP
Acetaminophen Related Compound J RS in the
▲
▲ (IRA 1-Jan-2023)
Standard solution (µg/mL)
System suitability solution: 20 µg/mL of USP CU = concentration of Acetaminophen in the Sample
Acetaminophen RS and 80 µg/mL each of USP solution (µg/mL)
Acetaminophen Related Compound B RS and USP
Acetaminophen Related Compound C RS in Calculate the percentage of acetaminophen related
compound B, acetaminophen related compound C,

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▲
methanol▲ (IRA 1-Jan-2023)
▲ (IRA 1-Jan-2023) and any unspecified impurity in the portion
▲
Standard solution: 1.25 µg/mL of USP Acetaminophen
Related Compound D RS and 0.25 µg/mL of USP of Acetaminophen taken:
Acetaminophen Related Compound J RS in
▲
methanol▲ (IRA 1-Jan-2023) ci Result = (rU/rS) × (CS/CU) × (1/F) × 100
Sample solution: 25 mg/mL of Acetaminophen in
rU = peak response of each specified or unspecified
▲
methanol▲ (IRA 1-Jan-2023) impurity from the Sample solution
Chromatographic system rS = peak response of acetaminophen related
(See Chromatography á621ñ, System Suitability.) compound D from the Standard solution
Mode: LC CS = concentration of USP Acetaminophen Related
Detector: UV 254 nm
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Compound D RS in the Standard solution
Column: 4.6-mm × 25-cm; 5-µm packing L7 (µg/mL)
Flow rate: 0.9 mL/min CU = concentration of Acetaminophen in the Sample
Column temperature: 40° solution (µg/mL)
Injection volume: 5 µL F = relative response factor for each impurity shown
System suitability in Table 4
Samples: System suitability solution and Standard solution
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[NOTE—▲The relative retention times in Table 3 are Acceptance criteria: See Table 4. [NOTE—The ▲▲ (IRA 1-Jan-2023)
provided as information that could aid in peak relative response factors in Table 4 (where applicable) are
assignment. The relative retention times are calculated relative to those of acetaminophen related
calculated relative to those of acetaminophen related compound D.]
compound D.]
Table 4
Table 3▲ (IRA 1-Jan-2023)
Relative Acceptance Crite-
Relative Response ria,
Retention Name Factor NMT (%)
Name Time
▲ ▲ ▲
▲ (IRA 1-Jan-2023) ▲ (IRA 1-Jan-2023) ▲ (IRA 1-Jan-2023)
Acetaminophen 0.43
Acetaminophen related com-
Acetaminophen related compound B 0.67 pound B▲▲ (IRA 1-Jan-2023) 1.2 0.05
Acetaminophen related compound C 0.71 Acetaminophen related com-
pound C▲▲ (IRA 1-Jan-2023) 0.38 0.05
Acetaminophen related compound D 1.0

Acetaminophen related compound J 1.73 Acetaminophen related com- ▲

—▲
pound D▲▲ (IRA 1-Jan-2023) (IRA 1-Jan-2023) 0.05

Suitability requirements Acetaminophen related com-

—
pound J▲▲ (IRA 1-Jan-2023) 0.001
Resolution: NLT 2.0 between acetaminophen and
acetaminophen related compound B; NLT 1.5 between ▲
Any▲ (IRA 1-Jan-2023)unspecified impur-
acetaminophen related compound B and ity 1.0 0.05
acetaminophen related compound C, System suitability Total impurities — 0.1
solution
Tailing factor: NMT 2.0 for acetaminophen related
compound D, Standard solution SPECIFIC TESTS
Relative standard deviation: NMT 5.0% for • LOSS ON DRYING á731ñ
acetaminophen related compound D, Standard solution Analysis: Dry at 105° to constant weight.
Acceptance criteria: NMT 0.5%

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Printed on: Thu Mar 30 2023, 09:48:36 AM(EST) Status: Currently Official on 30-Mar-2023 DocId: GUID-33AD0880-7404-4169-BDD5-F74D808EE77F_5_en-US
Printed by: MICHEL NTAMBWE Official Date: Official as of 01-Jan-2023 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: h2802 DOI: https://doi.org/10.31003/USPNF_M150_05_01
3

ADDITIONAL REQUIREMENTS USP Acetaminophen Related Compound C RS

• PACKAGING AND STORAGE: Preserve in tight, light-resistant N-(2-Hydroxyphenyl)acetamide.
containers, and store at room temperature. Protect from C8H9NO2 151.16
moisture and heat. USP Acetaminophen Related Compound D RS
N-Phenylacetamide.
Change to read: C8H9NO 135.17
USP Acetaminophen Related Compound J RS
• USP REFERENCE STANDARDS á11ñ N-(4-Chlorophenyl)acetamide (p-chloroacetanilide).
USP Acetaminophen RS C8H8ClNO 169.61
USP Acetaminophen Related Compound B RS USP 4-Aminophenol RS
▲
N-(4-Hydroxyphenyl)propionamide; also C6H7NO 109.13
known as▲ (IRA 1-Jan-2023)N-(4-Hydroxyphenyl)
propanamide.
C9H11NO2 165.19

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