Printed on: Fri Jan 05 2024, 10:11:15 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-62057678-318E-4547-9021-4120852719F0_5_en-US

Printed by: USP NF Official Date: Official as of 01-Aug-2023 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: p3xkw DOI: https://doi.org/10.31003/USPNF_M258_05_01
1

Sample solution: Dilute 5.0 mL of the Sample stock solution

Acetaminophen and Codeine with Mobile phase to 50 mL, and pass a portion through a
Phosphate Capsules filter of 1-µm pore size.
Chromatographic system
DEFINITION (See Chromatography á621ñ, System Suitability.)
Acetaminophen and Codeine Phosphate Capsules contain Mode: LC
NLT 90.0% and NMT 110.0% of the labeled amount of Detector: UV 214 nm
acetaminophen (C8H9NO2) and codeine phosphate Column: 4.6-mm × 25-cm; 5-µm packing L1
(C18H21NO3 · H3PO4 · ½H2O). Flow rate: 1.5 mL/min
Injection volume: 30 µL
IDENTIFICATION System suitability
• A. The retention times of the major peaks of the Sample Sample: Standard solution
solution correspond to those of the Standard solution, as Suitability requirements
obtained in the Assay. Resolution: NLT 2.0 between acetaminophen and
• B. THIN-LAYER CHROMATOGRAPHY codeine
Standard solution: 12 mg/mL each of USP Acetaminophen Relative standard deviation: NMT 2.0% for
RS and USP Codeine Phosphate RS in methanol acetaminophen; NMT 3.0% for codeine
Sample solution: Transfer a portion of Capsule contents, Analysis
equivalent to 12 mg of codeine phosphate, to a separator. Samples: Standard solution and Sample solution
Add 5 mL of water, 1 mL of ammonium hydroxide, and Calculate the percentage of the labeled amount of
5 mL of methylene chloride. Shake for 1 min, and allow the acetaminophen (C8H9NO2) in the portion of Capsules
layers to separate. Use the clear lower layer. taken:
Chromatographic system

al
(See Chromatography á621ñ, General Procedures, Thin-Layer Result = (r U/r S) × (C S/C U) × 100
Chromatography.)
Adsorbent: 0.25-mm layer of chromatographic silica gel rU = peak response of acetaminophen from the
mixture Sample solution
Application volume: 10 µL rS = peak response of acetaminophen from the
Developing solvent system: Methanol and ammonium
hydroxide (49:1)
Analysis
ci CS
Standard solution
= concentration of USP Acetaminophen RS in the
Standard solution (mg/mL)
Samples: Standard solution and Sample solution CU = nominal concentration of acetaminophen in the
Allow the spots to dry after applying each sample to the Sample solution (mg/mL)
ffi
adsorbent. Develop the chromatogram in the Developing
solvent system until the solvent front has moved Calculate the percentage of the labeled amount of codeine
three-fourths of the length of the plate. Remove the plate phosphate (C18H21NO3 · H3PO4 · ½H2O) in the portion of
from the developing chamber, mark the solvent front, and Capsules taken:
allow the solvent to evaporate. Locate the spots on the
plate by examination under short-wavelength UV light. Result = (r U/r S) × (C S/C U) × (M r1/M r2) × 100
O

Acceptance criteria: The R F values of the two principal

spots of the Sample solution correspond to those of the rU = peak response of codeine from the Sample
Standard solution. solution
rS = peak response of codeine from the Standard
ASSAY solution
• PROCEDURE CS = concentration of USP Codeine Phosphate RS in
Solution A: Dissolve 2.04 g of monobasic potassium the Standard solution (mg/mL)
phosphate in 950 mL of water. Add 2 mL of triethylamine, CU = nominal concentration of codeine phosphate in
adjust with phosphoric acid to a pH of 2.35, and dilute with the Sample solution (mg/mL)
water to 1000 mL. M r1 = molecular weight of codeine phosphate, 406.37
Mobile phase: Methanol and Solution A (8:92)
M r2 = molecular weight of anhydrous codeine
Codeine phosphate standard stock solution: 0.3 mg/mL phosphate, 397.37
of USP Codeine Phosphate RS in Mobile phase
Standard solution: 0.3 mg/mL of USP Acetaminophen RS Acceptance criteria
and 0.3J mg/mL of codeine phosphate in Mobile phase, Acetaminophen: 90.0%–110.0%
prepared as follows. Transfer an appropriate amount of USP Codeine phosphate: 90.0%–110.0%
Acetaminophen RS and a suitable volume (multiplied by J)
of Codeine phosphate standard stock solution (J being the PERFORMANCE TESTS
ratio of the labeled amount, in mg, of codeine phosphate • DISSOLUTION á711ñ
to that of acetaminophen) to a suitable volumetric flask. Medium: 0.01 N hydrochloric acid; 900 mL
Dilute with Mobile phase to volume. Apparatus 2: 50 rpm
Sample stock solution: Nominally 3.0 mg/mL of Time: 30 min
acetaminophen and 3.0J mg/mL of codeine phosphate Analysis: Determine the percentage of the labeled amount
(equivalent to 2.93J mg/mL of anhydrous codeine of acetaminophen (C8H9NO2) and codeine phosphate
phosphate) in Mobile phase, prepared as follows. Transfer a (C18H21NO3 · H3PO4 · ½H2O) dissolved by using the method
portion of the combined contents, equivalent to 300 mg of set forth in the Assay, except use 0.01 N hydrochloric acid
acetaminophen, from NLT 20 Capsules, to a 100-mL to prepare the Codeine phosphate standard stock solution,
volumetric flask. Add 75 mL of Mobile phase, and sonicate and make any other necessary volumetric adjustments.
for 10 min. Dilute with Mobile phase to volume.

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Printed on: Fri Jan 05 2024, 10:11:15 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-62057678-318E-4547-9021-4120852719F0_5_en-US
Printed by: USP NF Official Date: Official as of 01-Aug-2023 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: p3xkw DOI: https://doi.org/10.31003/USPNF_M258_05_01
2

Tolerances: NLT 75% (Q) of the labeled amount of CS = concentration of USP Acetaminophen RS in the
acetaminophen (C8H9NO2) and codeine phosphate Standard solution (mg/mL)
(C18H21NO3 · H3PO4 · ½H2O) is dissolved. F = dilution volume, 1000 mL

Change to read: Calculate the quantity, in mg, of codeine phosphate

(C18H21NO3 · H3PO4 · ½H2O) in the Capsule taken:
• UNIFORMITY OF DOSAGE UNITS á905ñ: ▲Meet the
requirements▲ (CN 1-Aug-2023) Result = (r U/r S) × C S × (M r1/M r2) × F
Procedure for content uniformity
Solution A, Mobile phase, Codeine phosphate standard rU = peak response of codeine from the Sample
stock solution, Standard solution, Chromatographic solution
system, and System suitability: Proceed as directed in rS = peak response of codeine from the Standard
the Assay. solution
Sample stock solution: Transfer the contents of 1 Capsule CS = concentration of USP Codeine Phosphate RS in
to a 100-mL volumetric flask. Add 75 mL of Mobile phase, the Standard solution (mg/mL)
and sonicate for 10 min. Dilute with Mobile phase to M r1 = molecular weight of codeine phosphate, 406.37
volume. M r2 = molecular weight of anhydrous codeine
Sample solution: Dilute 5.0 mL of the Sample stock phosphate, 397.37
solution with Mobile phase to 50 mL, and pass a portion F = dilution volume, 1000 mL
through a suitable filter of 1-µm pore size.
▲
Analysis ▲ (CN 1-Aug-2023)
Samples: Standard solution and Sample solution IMPURITIES

al
Calculate the quantity, in mg, of acetaminophen • 4-AMINOPHENOL IN ACETAMINOPHEN-CONTAINING DRUG
(C8H9NO2) in the Capsule taken: PRODUCTS á227ñ: Meet the requirements
Result = (r U/r S) × C S × F ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight, light-resistant
rU = peak response of acetaminophen from the containers, and store at controlled room temperature.
rS
Sample solution
= peak response of acetaminophen from the
Standard solution
ci • USP REFERENCE STANDARDS á11ñ
USP Acetaminophen RS
USP Codeine Phosphate RS
ffi
O

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