Interim Revision Announcement
Official May 1, 2014
Acetaminophen
1
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
.
Acetaminophen
C8H9NO2
Acetamide, N-(4-hydroxyphenyl)-;
4′-Hydroxyacetanilide [103-90-2].
151.16
IMPURITIES
• RESIDUE ON IGNITION 〈281〉: NMT 0.1%
• HEAVY METALS, Method II 〈231〉: NMT 10 ppm
Change to read:
DEFINITION
Acetaminophen contains NLT 98.0% and NMT 102.0% of
acetaminophen (C8H9NO2), calculated on the dried basis.
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197K〉
• 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
• LIMIT OF FREE •4-AMINOPHENOL• (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 •4-aminophenol• (IRA 1-May-2014) and acetaminophen are 0.6 and 1.0,
respectively.]
Suitability requirements
Relative standard deviation: NMT 5.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of 4-aminophenol •• (IRA 1-May2014) in the portion of Acetaminophen taken:
.
.
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)
0.0
3.0
7.0
7.1
10.0
Solution A
(%)
99
99
19
99
99
Solution B
(%)
1
1
81
1
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
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: •UV 230 nm• (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 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, •glacial• (IRA 1-May-2014) acetic acid (50:950:1)
Solution B: Methanol, water, •glacial• (IRA 1-May-2014)
acetic acid (500:500:1)
Mobile phase: See Table 2.
.
.
Table 2
.
Result = (rU/rS) × (CS/CU) × 100
rU
rS
= peak response from the Sample solution
= peak response from the Standard solution
Time
(min)
0
8
53
58
59
73
Solution A
(%)
82
82
0
0
82
82
Solution B
(%)
18
18
100
100
18
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
2014 The United States Pharmacopeial Convention All Rights Reserved.
2
Interim Revision Announcement
Official May 1, 2014
Acetaminophen
Sample solution: 25 mg/mL of Acetaminophen in
Diluent
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
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.
•[NOTE—The relative retention times and relative response factors in Table 3 (where applicable) are calculated relative to those of acetaminophen related compound D.]• (IRA 1-May-2014)
Table 3
Relative
Retention
Time
••
.
Name
Acetaminophen
Acetaminophen related compound Ba
Acetaminophen related compound
Cb
Acetaminophen related compound
Dc
Acetaminophen related compound Jd
Individual unspecified impurity
Total impurities
.
.
2014)
0.43
Relative
Response
Factor
—
•1.2•
.
.
.
(IRA 1-May-
0.67
(IRA 1-
May-2014)
•0.38•
(IRA 1-
.
0.71
May-2014)
1.0
1.73
1.0
—
—
•1.0•
—
—
.
Acceptance
Criteria,
NMT (%)
—
0.05
0.05
0.05
0.001
(IRA 1-
May-2014)
0.05
0.1
N-(4-Hydroxyphenyl)propanamide.
N-(2-Hydroxyphenyl)acetamide.
c N-Phenylacetamide.
d N-(4-Chlorophenyl)acetamide (p-chloroacetanilide).
a
.
b
.
.
•
.
.
•
.
(IRA 1-May-2014)
SPECIFIC TESTS
• LOSS ON DRYING 〈731〉
Analysis: Dry at 105° to constant weight.
Acceptance criteria: NMT 0.5%
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〉
USP Acetaminophen RS
USP Acetaminophen Related Compound B RS
N-(4-Hydroxyphenyl)propanamide.
C9H11NO2 165.19
USP Acetaminophen Related Compound C RS
N-(2-Hydroxyphenyl)acetamide.
C8H9NO2
151.16
USP Acetaminophen Related Compound D RS
N-Phenylacetamide.
C8H9NO
135.17
USP Acetaminophen Related Compound J RS
N-(4-Chlorophenyl)acetamide (p-chloroacetanilide).
C8H8ClNO
169.61
USP 4-Aminophenol RS
C6H7NO
109.13
.
2014 The United States Pharmacopeial Convention All Rights Reserved.