Acetaminophen
C8H9NO2 151.16
Acetamide, N-(4-hydroxyphenyl)-;
4¢-Hydroxyacetanilide
[103-90-2].
231
:
NMT 10 ppm(Official 1-Dec-2015)
(a seet'' a min' oh fen).
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C8H9NO2 151.16
Acetamide, N-(4-hydroxyphenyl)-;
4¢-Hydroxyacetanilide
[103-90-2].DEFINITION
Acetaminophen contains NLT 98.0% and NMT 102.0% of acetaminophen (C8H9NO2), calculated on the dried basis.
IDENTIFICATION
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
Change to read:
• Procedure
Use low-actinic glassware for preparation of the Sample solution.
Solution A:
1.7 g/L of monobasic potassium phosphate and 1.8 g/L of dibasic sodium phosphate, anhydrous
Solution B:
Methanol
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0.0 | 99 | 1 |
| 3.0 | 99 | 1 |
| 7.0 | 19 | 81 |
| 7.1 | 99 | 1 |
| 10.0 | 99 | 1 |
Standard solution:
0.1 mg/mL of USP Acetaminophen RS in methanol
Sample solution:
0.1 mg/mL of Acetaminophen in methanol
Chromatographic system
Mode:
LC
Detector:
(IRA 1-May-2014)
Column:
4.6-mm × 10-cm; 3.5-µm packing L7
Column temperature:
35
Flow rate:
1.0 mL/min
Injection volume:
5 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 1.0%
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 from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Acetaminophen RS in the Standard solution (mg/mL) |
| CU | = | = concentration of Acetaminophen in the Sample solution (mg/mL) |
Acceptance criteria:
98.0%–102.0% on the dried basis
IMPURITIES
• Residue on Ignition 281:
NMT 0.1%
281:
NMT 0.1%
Delete the following:
231:
NMT 10 ppm(Official 1-Dec-2015)
Change to read:
• Limit of Free
(IRA 1-May-2014)
Solution A, Solution B, Mobile phase, and Chromatographic system:
Proceed as directed in the Assay.
Standard solution:
1.25 µg/mL of USP 4-Aminophenol RS in methanol
Sample solution:
25 mg/mL of Acetaminophen in methanol
System suitability
Sample:
Standard solution
[Note—The relative retention times for
(IRA 1-May-2014)
Suitability requirements
Relative standard deviation:
NMT 5.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of 4-aminophenol
(IRA 1-May-2014)
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of 4-aminophenol from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP 4-Aminophenol RS in the Standard solution (µg/mL) |
| CU | = | = concentration of Acetaminophen in the Sample solution (µg/mL) |
Acceptance criteria:
NMT 0.005%
Change to read:
• Organic Impurities
Solution A:
Methanol, water,
(IRA 1-May-2014)
Solution B:
Methanol, water,
(IRA 1-May-2014)
Mobile phase:
See Table 2.
Table 2
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 82 | 18 |
| 8 | 82 | 18 |
| 53 | 0 | 100 |
| 58 | 0 | 100 |
| 59 | 82 | 18 |
| 73 | 82 | 18 |
Diluent:
Methanol
System suitability solution:
20 µg/mL of USP Acetaminophen RS and 80 µg/mL each of USP Acetaminophen Related Compound B RS and USP Acetaminophen Related Compound C RS in Diluent
Standard solution:
1.25 µg/mL of USP Acetaminophen Related Compound D RS and 0.25 µg/mL of USP Acetaminophen Related Compound J RS in Diluent
Sample solution:
25 mg/mL of Acetaminophen in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Flow rate:
0.9 mL/min
Column temperature:
40
Injection volume:
5 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—See Table 3 for relative retention time values. ]
Suitability requirements
Tailing factor:
NMT 2.0 for acetaminophen related compound D, Standard solution
Resolution:
NLT 2.0 between acetaminophen and acetaminophen related compound B; NLT 1.5 between acetaminophen related compound B and acetaminophen related compound C, System suitability solution
Relative standard deviation:
NMT 5.0% for acetaminophen related compound D, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of acetaminophen related compound J in the portion of Acetaminophen taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of acetaminophen related compound J from the Sample solution |
| rS | = | = peak response of acetaminophen related compound J from the Standard solution |
| CS | = | = concentration of USP Acetaminophen Related Compound J RS in the Standard solution (µg/mL) |
| CU | = | = concentration of Acetaminophen in the Sample solution (µg/mL) |
Calculate the percentage of acetaminophen related compounds B, C, and D and any unspecified impurity in the portion of Acetaminophen taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each specified or unspecified impurity from the Sample solution |
| rS | = | = peak response of acetaminophen related compound D from the Standard solution |
| CS | = | = concentration of USP Acetaminophen Related Compound D RS in the Standard solution (µg/mL) |
| CU | = | = concentration of Acetaminophen in the Sample solution (µg/mL) |
| F | = | = relative response factor for each impurity shown in Table 3 |
Acceptance criteria:
See Table 3.
(IRA 1-May-2014)
Table 3
| Name
|
Relative Retention Time (IRA 1-May-2014)
|
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Acetaminophen | 0.43 | — | — |
| Acetaminophen related compound Ba |
0.67 |
(IRA 1-May-2014)
|
0.05 |
| Acetaminophen related compound Cb |
0.71 |
(IRA 1-May-2014)
|
0.05 |
| Acetaminophen related compound Dc |
1.0 | 1.0 | 0.05 |
| Acetaminophen related compound Jd |
1.73 | — | 0.001 |
| Individual unspecified impurity | — |
(IRA 1-May-2014)
|
0.05 |
| Total impurities | — | — | 0.1 |
|
a
N-(4-Hydroxyphenyl)propanamide.
b
N-(2-Hydroxyphenyl)acetamide.
c
N-Phenylacetamide.
d
N-(4-Chlorophenyl)acetamide (p-chloroacetanilide).
(IRA 1-May-2014)
|
|||
SPECIFIC TESTS
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store at room temperature. Protect from moisture and heat.
• USP Reference Standards 11
11
USP Acetaminophen RS 
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USP Acetaminophen Related Compound B RS
N-(4-Hydroxyphenyl)propanamide.
C9H11NO2 165.19
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N-(4-Hydroxyphenyl)propanamide.
C9H11NO2 165.19
USP Acetaminophen Related Compound C RS
N-(2-Hydroxyphenyl)acetamide.
C8H9NO2 151.16
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N-(2-Hydroxyphenyl)acetamide.
C8H9NO2 151.16
USP Acetaminophen Related Compound D RS
N-Phenylacetamide.
C8H9NO 135.17
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N-Phenylacetamide.
C8H9NO 135.17
USP Acetaminophen Related Compound J RS
N-(4-Chlorophenyl)acetamide (p-chloroacetanilide).
C8H8ClNO 169.61
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N-(4-Chlorophenyl)acetamide (p-chloroacetanilide).
C8H8ClNO 169.61
USP 4-Aminophenol RS
C6H7NO 109.13
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C6H7NO 109.13
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Alan R Potts, PhD
Principal Scientific Liaison (301) 816-8364 |
(SM22010) Monographs - Small Molecules 2 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP38–NF33 Page 2004
Pharmacopeial Forum: Volume No. 39(6)