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156 by UIW1 on Tue Nov 13 01:45:49 EST 2018

8266 Acetaminophen / Official Monographs First Supplement to USP 41–NF 36

Analysis Delete the following:

Samples: Standard solution and Sample solution
Calculate the percentage of 4-aminophenol in the por- ■ • B. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST
tion of Oral Suspension taken:
.

〈201〉
Sample solution: Nominally 1 mg/mL of acetamino-
Result = (rU/rS) × (CS/CU) × 100 phen prepared as follows. Triturate 50 mg of acetamin-
rU = peak response of 4-aminophenol from the ophen from powdered Tablets in 50 mL of methanol,
Sample solution and filter. Use the clear filtrate.
rS = peak response of 4-aminophenol from the Chromatographic system
Standard solution Developing solvent system: Methylene chloride and
CS = concentration of USP 4-Aminophenol RS in methanol (4:1)
the Standard solution (mg/mL) Acceptance criteria: Meet the requirements■1S (USP41)
CU = nominal concentration of acetaminophen in
the Sample solution (mg/mL) Add the following:
Calculate the percentage of acetaminophen dimer or
any unspecified impurity in the portion of Oral ■ • B. The UV spectrum of the acetaminophen peak of the
Suspension taken:
.

Sample solution corresponds to that of the Standard solu-

tion, as obtained in the Assay.■1S (USP41)
Result = (rU/rS) × (CS/CU) × 100
ASSAY
rU = peak response of acetaminophen dimer or any
unspecified impurity from the Sample solution
rS = peak response of acetaminophen from the Change to read:
Standard solution
CS = concentration of USP Acetaminophen RS in • PROCEDURE
■Solution A: 1% (v/v) glacial acetic acid in water
the Standard solution (mg/mL) .

CU = nominal concentration of acetaminophen in Solution B: Methanol

the Sample solution (mg/mL) Mobile phase: See Table 1. Return to original condi-
Acceptance criteria: See Table 3. The reporting thresh- tions and re-equilibrate the system for 4 min.
old is 0.05% for any impurities.
Table 1
Table 3 Time Solution A Solution B
Relative Acceptance (min) (%) (%)
Retention Criteria, 0.0 90 10
Name Time NMT (%) 4.0 90 10
4-Aminophenol 0.28 0.15 4.1 20 80
Acetaminophen 1.0 — 6.0 20 80
Acetaminophen
dimera 1.57 0.15 Diluent: Methanol and water (10:90)
Standard solution: 0.01 mg/mL of USP Acetaminophen
.

Any
unspecified — RS in Diluent
impurity 0.15 Sample stock solution: Nominally 0.1 mg/mL of acet-
Total impurities — 2.0
aminophen in Diluent prepared as follows. Transfer an
a N,N’-(6,6’-Dihydroxy-[1,1’-biphenyl]-3,3’-diyl)diacetamide.
appropriate amount of acetaminophen from NLT 10
.

Tablets to a suitable volumetric flask and dilute with

■1S (USP41)
Diluent to volume. Centrifuge or pass a portion of this
solution through a suitable filter. [NOTE—Sonication or
SPECIFIC TESTS shaking may be necessary.]
• PH 〈791〉: 4.0–6.9 Sample solution: Nominally 0.01 mg/mL of acetamino-
phen in Diluent from the Sample stock solution. Pass a
ADDITIONAL REQUIREMENTS portion of this solution through a suitable filter.
• PACKAGING AND STORAGE: Preserve in tight containers, Chromatographic system
and store at controlled room temperature. (See Chromatography 〈621〉, System Suitability.)
• USP REFERENCE STANDARDS 〈11〉 Mode: LC
USP Acetaminophen RS Detector: UV 243 nm. For Identification B, use a diode
USP 4-Aminophenol RS array detector in the range of 220–400 nm.
Column: 3.0-mm × 10-cm; 3.5-µm packing L1
Column temperature: 40°
Flow rate: 0.5 mL/min
.

Injection volume: 10 µL
Acetaminophen Tablets System suitability
Sample: Standard solution
DEFINITION Suitability requirements
Acetaminophen Tablets contain NLT 90.0% and NMT Tailing factor: NMT 2.0
110.0% of the labeled amount of acetaminophen Relative standard deviation: NMT 2.0%
(C8H9NO2). Analysis
Samples: Standard solution and Sample solution
IDENTIFICATION Calculate the percentage of the labeled amount of acet-
• A. The retention time of the acetaminophen peak of the aminophen (C8H9NO2) in the portion of Tablets taken:
Sample solution corresponds to that of the Standard solu-
tion, as obtained in the Assay. Result = (rU/rS) × (CS/CU) × 100

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Accessed from 122.3.17.156 by UIW1 on Tue Nov 13 01:45:49 EST 2018

First Supplement to USP 41–NF 36 Official Monographs / Acetaminophen 8267

rU = peak response of acetaminophen from the Table 2 (Continued)

Sample solution
rS = peak response of acetaminophen from the
Standard solution
CS = concentration of USP Acetaminophen RS in
the Standard solution (mg/mL)
CU = nominal concentration of acetaminophen in
the Sample solution (mg/mL)■1S (USP41)
Acceptance criteria: 90.0%–110.0%
PERFORMANCE TESTS
• DISSOLUTION 〈711〉
Medium: pH 5.8 phosphate buffer (see Reagents, Indica-
tors, and Solutions—Buffer Solutions); 900 mL
Apparatus 2: 50 rpm
Time: 30 min
Standard solution: A known concentration of USP
Acetaminophen RS in Medium
Sample solution: A filtered portion of the solution
under test, suitably diluted with Medium to obtain a
concentration similar to that of the Standard solution
Instrumental conditions
Mode: UV
Analytical wavelength: Maximum absorbance at
about 243 nm
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of acet-
aminophen (C8H9NO2) dissolved.
Tolerances: NLT 80% (Q) of the labeled amount of
acetaminophen (C8H9NO2) is dissolved.
For Tablets labeled as chewable
Medium: pH 5.8 phosphate buffer (see Reagents, In-
dicators, and Solutions—Buffer Solutions); 900 mL
Apparatus 2: 75 rpm
Time: 45 min
Standard solution, Sample solution, Instrumental
conditions, and Analysis: Proceed as directed above.
Tolerances: NLT 75% (Q) of the labeled amount of
acetaminophen (C8H9NO2) is dissolved.
• UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the
requirements
IMPURITIES
Delete the following:
■ • 4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG
.
Time Solution A Solution C
(min) (%) (%)
10 10 90
11 10 90
Diluent: Methanol and Buffer (5:95)
Sensitivity solution: 0.000175 mg/mL of USP 4-Ami-
nophenol RS in Diluent. Sonicate to dissolve, if
necessary.
Standard solution: 0.00175 mg/mL of USP 4-Ami-
nophenol RS and 0.0035 mg/mL of USP Acetamino-
phen RS in Diluent. Sonicate to dissolve, if necessary.
Sample stock solution: Nominally 5 mg/mL of acet-
aminophen in Diluent from NLT 10 Tablets. [NOTE—It is
recommended to shake on a flat bed at low speed (180
oscillations/min) to dissolve, if necessary.]
Sample solution: Nominally 3.5 mg/mL of acetamino-
phen in Diluent prepared as follows. Pass a portion of
the Sample stock solution through a suitable filter of 0.2-
µm pore size. Discard the first 2 mL of the filtrate. Di-
lute a suitable volume of the filtrate with Diluent to
volume.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 272 nm. For Identification B, use a diode
array detector in the range of 200–400 nm.
Column: 4.6-mm × 15-cm; 3-µm packing L1
Column temperature: 40°
Flow rate: 0.9 mL/min
Injection volume: 25 µL
System suitability
Samples: Sensitivity solution and Standard solution
Suitability requirements
Relative standard deviation: NMT 5.0% for 4-ami-
nophenol and acetaminophen, Standard solution
Signal-to-noise ratio: NLT 10 for 4-aminophenol,
Sensitivity solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of 4-aminophenol in the por-
tion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of 4-aminophenol from the

Sample solution
PRODUCTS 〈227〉: Meet the requirements■1S (USP41) rS = peak response of 4-aminophenol from the
Standard solution
Add the following: CS = concentration of USP 4-Aminophenol RS in
the Standard solution (mg/mL)
■ • ORGANIC IMPURITIES CU = nominal concentration of acetaminophen in
.

It is suggested to protect all solutions containing acet- the Sample solution (mg/mL)
aminophen or 4-aminophenol from light. Calculate the percentage of any unspecified impurity in
Buffer: Dissolve 1.9 g of ammonium formate in 1 L of the portion of Tablets taken:
water. Add 1.0 mL of formic acid. Result = (rU/rS) × (CS/CU) × 100
Solution A: Dissolve 3.1 g of ammonium acetate in 1 L
of water. Add 1.0 mL of trifluoroacetic acid. rU = peak response of any unspecified impurity
Solution B: Acetonitrile, methanol, and water from the Sample solution
(10:75:15) rS = peak response of acetaminophen from the
Solution C: Dissolve 3.1 g of ammonium acetate in Standard solution
1000 mL of Solution B. Add 1.0 mL of trifluoroacetic CS = concentration of USP Acetaminophen RS in
acid. the Standard solution (mg/mL)
Mobile phase: See Table 2. Return to original condi- CU = nominal concentration of acetaminophen in
tions and re-equilibrate the system for 4 min. the Sample solution (mg/mL)
Acceptance criteria: See Table 3.
Table 2
Time Solution A Solution C
(min) (%) (%)
0 97 3
5 70 30

Official from August 1, 2018

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8268 Acetaminophen / Official Monographs First Supplement to USP 41–NF 36

Table 3 Mobile phase: Methanol and Buffer ■(70:30)■1S (USP41)

.

Relative Acceptance
System suitability stock solution A: 1 mg/mL of USP
Retention Criteria,
Amitriptyline Related Compound A RS in methanol
Name Time NMT (%)
System suitability stock solution B: 0.4 mg/mL of USP
Amitriptyline Hydrochloride RS, 0.6 mg/mL each of USP
4-Aminophenol 0.53 0.15 Amitriptyline Related Compound B RS, USP
Acetaminophen 1.0 — Cyclobenzaprine Hydrochloride RS, and USP Nor-
Any unspecified impurity — 0.15 triptyline Hydrochloride RS in Mobile phase
Total impurities — 0.60 Standard solution: 0.2 mg/mL of USP Amitriptyline Hy-
drochloride RS in Mobile phase
■1S (USP41) System suitability solution: ■0.5 µg/mL of USP Ami-
.

triptyline Related Compound A RS, 1 µg/mL of USP

ADDITIONAL REQUIREMENTS Amitriptyline Hydrochloride RS, and 1.5 µg/mL each of
• PACKAGING AND STORAGE: Preserve in tight containers, USP Amitriptyline Related Compound B RS, USP
and store at controlled room temperature. Cyclobenzaprine Hydrochloride RS, and USP Nor-
• LABELING: Label Tablets that must be chewed to indicate triptyline Hydrochloride RS■1S (USP41) from suitable
that they are to be chewed before swallowing. volumes of Standard solution, System suitability stock so-
lution A, and System suitability stock solution B in Mobile
Change to read: phase
Sample solution: 0.2 mg/mL of Amitriptyline Hydro-
• USP REFERENCE STANDARDS 〈11〉 chloride in Mobile phase
USP Acetaminophen RS Chromatographic system
■USP 4-Aminophenol RS (See Chromatography 〈621〉, System Suitability.)
Mode: LC
.

4-Aminophenol.
C6H7NO 109.13■1S (USP41) Detector: UV 215 nm
Column: 4.6-mm × 25-cm; 5-µm packing L7
Column temperature: 45°
Flow rate: 1.5 mL/min
Injection volume: 20 µL
Run time: ■NLT■1S (USP41) 1.5 times the retention time
.

Amitriptyline Hydrochloride .

of amitriptyline
System suitability
Samples: Standard solution and System suitability
solution
[NOTE—For relative retention times, see Table 1.]
Suitability requirements
Resolution: NLT 1.5 between amitriptyline related
compound B and nortriptyline, System suitability
solution
Relative standard deviation: ■NMT 0.73%■1S (USP41)
.

C20H23N · HCl 313.86 for amitriptyline, Standard solution

1-Propanamine, 3-(10,11-dihydro-5H-dibenzo[a,
d]cyclohepten-5-ylidene)-N,N-dimethyl-, hydrochloride;
10,11-Dihydro-N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-
∆5,γ-propylamine hydrochloride [549-18-8].
.
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of amitriptyline hydrochloride

(C20H23N · HCl) in the portion of Amitriptyline Hydro-

chloride taken:
DEFINITION
Amitriptyline Hydrochloride contains NLT 98.0% and NMT Result = (rU/rS) × (CS/CU) × 100
102.0% of amitriptyline hydrochloride (C20H23N · HCl),
calculated on the dried basis. rU = peak response from the Sample solution
rS = peak response from the Standard solution
IDENTIFICATION CS = concentration of USP Amitriptyline
Hydrochloride RS in the Standard solution
Change to read: (mg/mL)
CU = concentration of Amitriptyline Hydrochloride
• A. INFRARED ABSORPTION ■〈197〉: [NOTE—Methods de- in the Sample solution (mg/mL)
Acceptance criteria: 98.0%–102.0% on the dried basis
.

scribed in 〈197K〉 or 〈197A〉 may be used.]■1S (USP41)

• B. The retention time of the major peak of the Sample IMPURITIES
solution corresponds to that of the Standard solution, as • RESIDUE ON IGNITION 〈281〉: NMT 0.1%
obtained in the Assay.
• C. IDENTIFICATION TESTS—GENERAL 〈191〉, Chemical Identifi-
cation Tests, Chloride: Meets the requirements Delete the following:
ASSAY •• HEAVY METALS, Method II 〈231〉: NMT 10 ppm• (Official 1-
.

Jan-2018)
Change to read:
Change to read:
• PROCEDURE
■ .

■1S (USP41) • ORGANIC IMPURITIES

Buffer: ■1.4 g/L of anhydrous dibasic sodium
.
■
■1S (USP41) Buffer, Mobile phase, Chromatographic sys-
phosphate■1S (USP41) in water, adjusted with ■1.5 M phos-
.

tem, and System suitability: Proceed as directed in

phoric acid TS■1S (USP41) to a pH of 7.7 the Assay.
Standard solution: Use the System suitability solution,
prepared as directed in the Assay.

Official from August 1, 2018

Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.