Printed on: Sat Jun 26 2021, 05:52:50 AM Official Status: Currently Official on 26-Jun-2021 DocId: 1_GUID-659E2246-6BCF-4101-9AEC-0302EA2E88CF_2_en-US

(EST)
Printed by: Nguyen Nhan Official Date: Official as of 01-May-2017 Document Type: USP @2021 USPC
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Result = (rU/rS) × (CS/CU) × 100

Acetaminophen and Codeine
Phosphate Oral Solution rU = peak response of acetaminophen from the
Sample solution
DEFINITION rS = peak response of acetaminophen from the
Acetaminophen and Codeine Phosphate Oral Solution Standard solution
contains NLT 90.0% and NMT 110.0% of the labeled CS = concentration of USP Acetaminophen RS in the
amount of acetaminophen (C8H9NO2) and codeine Standard solution (mg/mL)
phosphate hemihydrate (C18H21NO3 · H3PO4 · ½H2O). CU = nominal concentration of acetaminophen in the
Sample solution (mg/mL)
IDENTIFICATION
• A. The retention times of the major peaks of the Sample Acceptance criteria: 90.0%–110.0%
solutions correspond to those of the Standard solutions, as • CODEINE PHOSPHATE
obtained in the Assays for Acetaminophen and Codeine Mobile phase: Dissolve 4.44 g of docusate sodium in
Phosphate. 1000 mL of a mixture of methanol, tetrahydrofuran,
• B. THIN-LAYER CHROMATOGRAPHY phosphoric acid, and water (600:40:1:360) with stirring,
Standard solution: 12 mg/mL each of USP and pass through a membrane filter of 0.45-µm or finer
Acetaminophen RS and USP Codeine Phosphate RS in pore size.
methanol Diluent: Methanol and water (3:7)
Sample solution: Transfer a volume of Oral Solution, Standard solution: 0.12 mg/mL of USP Codeine
equivalent to 12 mg of codeine phosphate, to a separator. Phosphate RS in Diluent
Add 1 mL of ammonium hydroxide and 5 mL of methylene Sample solution: Nominally 0.12 mg/mL of codeine
chloride. Shake for 1 min, and allow the layers to separate. phosphate hemihydrate in Diluent, prepared by adding a

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Use the clear lower layer. volume of Oral Solution, equivalent to 12 mg of codeine
Developing solvent system: Methanol and ammonium phosphate hemihydrate, to a 100-mL volumetric flask.
hydroxide (49:1) Dilute with Diluent to volume.
Chromatographic system Chromatographic system
(See Chromatography á621ñ, Thin-Layer Chromatography.) (See Chromatography á621ñ, System Suitability.)
Mode: TLC
Adsorbent: 0.25-mm layer of chromatographic silica gel
mixture
ci Mode: LC
Detector: UV 280 nm
Column: 3.9-mm × 30-cm; packing L1
Application volume: 10 µL Flow rate: 1.5 mL/min
Analysis Injection volume: 10 µL
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Samples: Standard solution and Sample solution System suitability
Develop the chromatogram in the Developing solvent Sample: Standard solution
system until the solvent front has moved three-fourths of Suitability requirements
the length of the plate. Locate the spots on the plate by Tailing factor: NMT 2.0
examination under short-wavelength UV light. Relative standard deviation: NMT 3.0%
Acceptance criteria: The RF values of the two principal spots Analysis
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of the Sample solution correspond to those of the Standard Samples: Standard solution and Sample solution
solution. Calculate the percentage of the labeled amount of codeine
phosphate hemihydrate (C18H21NO3 · H3PO4 · ½H2O) in
ASSAY
• ACETAMINOPHEN the portion of Oral Solution taken:
Mobile phase: Methanol and water (3:7) Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
Standard solution: 0.48 mg/mL of USP Acetaminophen RS
in Mobile phase rU = peak response of codeine phosphate from the
Sample solution: Nominally 0.48 mg/mL of Sample solution
acetaminophen in Mobile phase, prepared by adding a rS = peak response of codeine phosphate from the
volume of Oral Solution, equivalent to 120 mg of Standard solution
acetaminophen, to a 250-mL volumetric flask. Dilute with CS = concentration of USP Codeine Phosphate RS in
Mobile phase to volume. the Standard solution (mg/mL)
Chromatographic system CU = nominal concentration of codeine phosphate in
(See Chromatography á621ñ, System Suitability.) the Sample solution (mg/mL)
Mode: LC Mr1 = molecular weight of codeine phosphate
Detector: UV 280 nm hemihydrate, 406.37
Column: 3.9-mm × 30-cm; packing L1 Mr2 = molecular weight of anhydrous codeine
Flow rate: 2 mL/min phosphate, 397.37
Injection volume: 10 µL
System suitability Acceptance criteria: 90.0%–110.0%
Sample: Standard solution
Suitability requirements PERFORMANCE TESTS
Tailing factor: NMT 1.5 • UNIFORMITY OF DOSAGE UNITS á905ñ
Relative standard deviation: NMT 2.0% For single-unit containers
Analysis Acceptance criteria: Meets the requirements
Samples: Standard solution and Sample solution • DELIVERABLE VOLUME á698ñ
Calculate the percentage of the labeled amount of For multiple-unit containers
acetaminophen (C8H9NO2) in the portion of Oral Solution Acceptance criteria: Meets the requirements
taken:

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Printed on: Sat Jun 26 2021, 05:52:50 AM Official Status: Currently Official on 26-Jun-2021 DocId: 1_GUID-659E2246-6BCF-4101-9AEC-0302EA2E88CF_2_en-US
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Printed by: Nguyen Nhan Official Date: Official as of 01-May-2017 Document Type: USP @2021 USPC
2

IMPURITIES ADDITIONAL REQUIREMENTS

• 4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG • PACKAGING AND STORAGE: Preserve in tight, light-resistant
PRODUCTS á227ñ: Meets the requirements containers, and store at controlled room temperature.
• USP REFERENCE STANDARDS á11ñ
SPECIFIC TESTS USP Acetaminophen RS
• PH á791ñ: 4.0–6.1 USP Codeine Phosphate RS
• ALCOHOL DETERMINATION á611ñ, Method II (if present):
90.0%–120.0% of the labeled quantity of alcohol
(C2H5OH), acetone being used as the internal standard

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