Acetaminophen Oral Suspension

Type of Posting Revision Bulletin, Postponement

Posting Date 27–Jul–2018
Official Date 01–Aug–2018
Expert Committee Chemical Medicines Monographs 6
Reason for Revision Compliance

In accordance with the Rules and Procedures of the 2015–2020 Council of Experts, the Chemical
Medicines Monographs 6 Expert Committee has revised the Acetaminophen Oral Suspension
monograph. The purpose for the revision is to postpone the implementation of the Assay and the test for
Organic Impurities and the omission of the test for 4-Aminophenol in Acetaminophen-Containing Drug
Products.

The Acetaminophen Oral Suspension Revision Bulletin supersedes the revision of the Acetaminophen
Oral Suspension monograph, which was published in the First Supplement to USP 41–NF 36 and is
scheduled to become official on 1–Aug–2018.

Should you have any questions, please contact Clydewyn M. Anthony, Ph.D., Senior Scientific Liaison
(301-816-8139 or [email protected]).

C206891-M190-CHM62015, Rev. 00 20180727

Revision Bulletin Acetaminophen 1
Official August 1, 2018
CS = concentration of USP Acetaminophen RS in
Acetaminophen Oral Suspension the Standard solution (mg/mL)
DEFINITION CU = nominal concentration of acetaminophen in
Acetaminophen Oral Suspension is a suspension of the Sample solution (mg/mL)
Acetaminophen in a suitable aqueous vehicle. It contains
NLT 90.0% and NMT 110.0% of the labeled amount of Acceptance criteria: 90.0%–110.0%▲ (RB 1-Aug-2018)
acetaminophen (C8H9NO2).
Change to read:
IDENTIFICATION
• A. INFRARED ABSORPTION á197Kñ • PROCEDURE
Sample: Transfer a volume of Oral Suspension, equivalent ▲
Solution A: Acetonitrile, trifluoroacetic acid, and water
to 240 mg of acetaminophen, to a separator. Add 50 mL (14: 0.1: 86)
of ethyl acetate, and shake. Filter the ethyl acetate extract Solution B: Acetonitrile, trifluoroacetic acid, and water (90:
through a funnel containing glass wool and 10 g of 0.1: 10)
anhydrous sodium sulfate. Collect the filtrate in a beaker, Mobile phase: See Table 1.
and evaporate on a steam bath to dryness. Dry the
residue under vacuum over silica gel. Table 1
Acceptance criteria: The crystals so obtained meet the Time Solution A Solution B
requirements. (min) (%) (%)

0.0 100 0
Add the following:
4.0 100 0
▲
• B. The retention time of the acetaminophen peak of the
Sample solution corresponds to that of the Standard 5.0 0 100
solution, as obtained in the Assay.▲ 1S (USP41) 6.0 100 0
ASSAY 10.0 100 0

Add the following:

Diluent: Methanol, phosphoric acid, and water (50: 0.1:
▲
• PROCEDURE 50)
Mobile phase: Methanol and water (1:3) Standard stock solution: 1.6 mg/mL of USP
Standard solution: 0.01 mg/mL of USP Acetaminophen Acetaminophen RS in Diluent
RS in Mobile phase Standard solution: 0.064 mg/mL of USP Acetaminophen
Sample stock solution: Nominally 0.5 mg/mL of RS in Solution A, from Standard stock solution
acetaminophen prepared as follows. Transfer 100 mg of Sample stock solution: Nominally 1.6 mg/mL of
acetaminophen from a volume of Oral Suspension, acetaminophen prepared as follows. Transfer a quantity
previously well shaken, to a 200-mL volumetric flask. Add equivalent to about 160 mg of acetaminophen from a
100 mL of Mobile phase, and shake by mechanical means volume of Oral Suspension, previously well shaken, to a
for 10 min. Dilute with Mobile phase to volume. 100-mL volumetric flask. Add 60 mL of Diluent, and shake
Sample solution: Nominally 0.01 mg/mL of by mechanical means for 30 min. Dilute with Diluent to
acetaminophen from the Sample stock solution in Mobile volume. Mix well. Allow the sample to settle, or
phase. Pass a portion of this solution through a filter of centrifuge.
0.5-µm pore size or finer, discarding the first 10 mL of the Sample solution: Nominally 0.064 mg/mL of
filtrate. Use the clear filtrate. acetaminophen in Solution A, from Sample stock solution
Chromatographic system Chromatographic system
(See Chromatography á621ñ, System Suitability.) (See Chromatography á621ñ, System Suitability.)
Mode: LC Mode: LC
Detector: UV 243 nm Detector: UV 214 nm
Column: 3.9-mm × 30-cm; packing L1 Column: 4.6-mm × 15-cm; 3.5-µm packing L11
Flow rate: 1.5 mL/min Flow rate: 1 mL/min
Injection volume: 10 µL Injection volume: 30 µL
System suitability System suitability
Sample: Standard solution Sample: Standard solution
Suitability requirements Suitability requirements
Column efficiency: NLT 1000 theoretical plates Tailing factor: NMT 2.0
Tailing factor: NMT 2.0 Relative standard deviation: NMT 2.0%
Relative standard deviation: NMT 2.0% Analysis
Analysis Samples: Standard solution and Sample solution
Samples: Standard solution and Sample solution Calculate the percentage of the labeled amount of
Calculate the percentage of the labeled amount of acetaminophen (C8H9NO2) in the portion of Oral
acetaminophen (C8H9NO2) in the portion of Oral Suspension taken:
Suspension taken:
Result = (rU/rS) × (CS/CU) × 100
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of acetaminophen from the
rU = peak response from the Sample solution Sample solution
rS = peak response from the Standard solution rS = peak response of acetaminophen from the
Standard solution

© 2018 The United States Pharmacopeial Convention All Rights Reserved.

C206891-M190-CHM62015, Rev. 00 20180727
2 Acetaminophen Revision Bulletin
Official August 1, 2018
CS = concentration of USP Acetaminophen RS in Column temperature: 40°
the Standard solution (mg/mL) Flow rate: 0.5 mL/min
CU = nominal concentration of acetaminophen in Injection volume: 2.5 µL
the Sample solution (mg/ System suitability
mL)▲ (Postponed on 1-Aug-2018) Samples: Sensitivity solution and Standard solution
[NOTE—See Table 3 for relative retention times.]
Acceptance criteria: 90.0%–110.0% Suitability requirements
Tailing factor: NMT 2.0 for acetaminophen and 4-
PERFORMANCE TESTS
• UNIFORMITY OF DOSAGE UNITS á905ñ aminophenol, Standard solution
For single-unit containers: Meets the requirements Relative standard deviation: NMT 5.0% for
• DELIVERABLE VOLUME á698ñ acetaminophen and 4-aminophenol, Standard solution
For multiple-unit containers: Meets the requirements Signal-to-noise ratio: NLT 10 for acetaminophen and
4-aminophenol, Sensitivity solution
IMPURITIES Analysis
Samples: Standard solution and Sample solution
Delete the following: Calculate the percentage of 4-aminophenol in the portion
of Oral Suspension taken:
▲
• 4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG
PRODUCTS á227ñ: Meets the Result = (rU/rS) × (CS/CU) × 100
requirements▲ (Postponed on 1-Aug-2018)
rU = peak response of 4-aminophenol from the
Add the following: Sample solution
rS = peak response of 4-aminophenol from the
▲
• ORGANIC IMPURITIES Standard solution
Solution A: 0.2% trifluoroacetic acid in water CS = concentration of USP 4-Aminophenol RS in
Solution B: 0.2% trifluoroacetic acid in water the Standard solution (mg/mL)
Mobile phase: See Table 2. CU = nominal concentration of acetaminophen in
the Sample solution (mg/mL)
Table 2
Time Solution A Solution B Calculate the percentage of acetaminophen dimer or any
(min) (%) (%) unspecified impurity in the portion of Oral Suspension
0.0 98 2 taken:
1.0 98 2 Result = (rU/rS) × (CS/CU) × 100
8.0 80 20
rU = peak response of acetaminophen dimer or
9.0 5 95 any unspecified impurity from the Sample
10.0 5 95 solution
rS = peak response of acetaminophen from the
10.5 98 2 Standard solution
13.0 98 2 CS = concentration of USP Acetaminophen RS in
the Standard solution (mg/mL)
CU = nominal concentration of acetaminophen in
Buffer: 10 mM sodium citrate dihydrate, with a pH of 4.0, the Sample solution (mg/mL)
prepared by adding 1.1 g of sodium citrate dihydrate and
1.3 g of citric acid monohydrate to a 1-L volumetric flask, Acceptance criteria: See Table 3. The reporting threshold
dissolving, and diluting with water to volume. Adjust with is 0.05% for any impurities.
sodium citrate dihydrate to increase the pH or with citric
acid monohydrate to decrease the pH, if necessary, to Table 3
achieve a pH of 4.0.
Relative Acceptance
Diluent: Acetonitrile and Buffer (10:90) Retention Criteria,
Sensitivity solution: 0.16 µg/mL of USP Acetaminophen Name Time NMT (%)
RS and 0.08 µg/mL of USP 4-Aminophenol RS in Diluent
4-Aminophenol 0.28 0.15
Standard solution: 1.6 µg/mL each of USP
Acetaminophen RS and USP 4-Aminophenol RS in Diluent Acetaminophen 1.0 —
Sample solution: Nominally 1.6 mg/mL of
Acetaminophen dimera 1.57 0.15
acetaminophen in Diluent prepared as follows. Transfer a
quantity equivalent to about 160 mg of acetaminophen Any
from a volume of Oral Suspension, previously well shaken, unspecified —
impurity 0.15
to a 100-mL volumetric flask. Add 60 mL of Diluent, and
shake by mechanical means for 1 h. Dilute with Diluent to Total impurities — 2.0
volume. Mix well. Pass a portion of this solution through
a N,N’-(6,6’-Dihydroxy-[1,1’-biphenyl]-3,3’-diyl)
a suitable filter.
Chromatographic system diacetamide.▲ (Postponed on 1-Aug-2018)
(See Chromatography á621ñ, System Suitability.)
Mode: LC SPECIFIC TESTS
Detector: UV 272 nm • PH á791ñ: 4.0–6.9
Column: 2.1-mm × 15-cm; 1.8-µm packing L1

© 2018 The United States Pharmacopeial Convention All Rights Reserved.

C206891-M190-CHM62015, Rev. 00 20180727
Revision Bulletin Acetaminophen 3
Official August 1, 2018
ADDITIONAL REQUIREMENTS • USP REFERENCE STANDARDS á11ñ
• PACKAGING AND STORAGE: Preserve in tight containers, USP Acetaminophen RS
and store at controlled room temperature. USP 4-Aminophenol RS

© 2018 The United States Pharmacopeial Convention All Rights Reserved.

C206891-M190-CHM62015, Rev. 00 20180727