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Acetaminophen and Codeine Phosphate Tablets
» Acetaminophen and Codeine Phosphate Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of acetaminophen (C8H9 NO2) and codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O).
Packaging and storage— Preserve in tight, light-resistant containers, and store at controlled room temperature.
Identification—
A: The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
B: A quantity of finely powdered Tablets, equivalent to about 12 mg of codeine phosphate, meets the requirements of Identification test B under Acetaminophen and Codeine Phosphate Capsules.
Dissolution 711
Medium: 0.01 N hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure— Determine the amounts of acetaminophen (C8H9NO2) and codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O) dissolved by employing the procedure set forth in the Assay, except to use 0.01 N hydrochloric acid to prepare the Codeine phosphate standard stock solution and to make any other necessary volumetric adjustments.
Tolerances— Not less than 75% (Q) of the labeled amounts of C8H9NO2 and C18H21NO3·H3PO4·½H2O is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Buffer solution, Mobile phase, Codeine phosphate standard stock solution, Standard preparation, and Chromatographic system— Prepare as directed in the Assay.
Sample preparation— Transfer 1 Tablet to a 100-mL volumetric flask, add about 75 mL of Mobile phase, and sonicate for 10 minutes. Dilute with Mobile phase to volume, and mix. Transfer 5.0 mL of the resulting solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a suitable 1-µm filter.
Procedure— Separately inject equal volumes (about 30 µL) of the Standard preparation and the Sample preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in each Tablet taken by the formula:
1000CA(rU / rS),
in which CA is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; and rU and rS are the peak responses obtained from the Sample preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O) in each Tablet taken by the formula:
(406.37/397.37)1000CC(rU / rS),
in which 406.37 and 397.37 are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate, respectively; CC is the concentration, in mg per mL, of USP Codeine Phosphate RS in the Standard preparation; and the other terms are as defined herein.
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Assay—
Buffer solution— Dissolve 2.04 g of monobasic potassium phosphate in about 950 mL of water. Add 2 mL of triethylamine, adjust with phosphoric acid to a pH of 2.35, dilute with water to 1000 mL, and mix.
Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and methanol (92:8). Make adjustments if necessary (see System Suitability under Chromatography 621).
Codeine phosphate standard stock solution— Dissolve an accurately weighed quantity of USP Codeine Phosphate RS in Mobile phase to obtain a solution having a known concentration of about 0.3 mg per mL.
Standard preparation— Transfer about 30 mg of USP Acetaminophen RS and 100 J mL of Codeine phosphate standard stock solution, J being the ratio of the labeled amount, in mg, of codeine phosphate hemihydrate to that of acetaminophen, to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 0.3 mg of acetaminophen and 0.3J mg of codeine phosphate hemihydrate per mL.
Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 300 mg of acetaminophen, to a 100-mL volumetric flask, add about 75 mL of Mobile phase, and sonicate for 10 minutes. Dilute with Mobile phase to volume, and mix. Transfer 5.0 mL of the resulting solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a suitable 1-µm filter.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between acetaminophen and codeine phosphate is not less than 2.0; and the relative standard deviation for replicate injections is not more than 2.0% and 3.0%, respectively.
Procedure— Separately inject equal volumes (about 30 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in the portion of Tablets taken by the formula:
(LCA / CU)(rU / rS),
in which L is the labeled quantity, in mg, of acetaminophen in each Tablet; CA is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; CU is the concentration, in mg per mL, of acetaminophen in the Assay preparation, based upon the labeled quantity per Tablet and the extent of dilution; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O) in the portion of Tablets taken by the formula:
(406.37/397.37)(LCC / CU)(rU / rS),
in which 406.37 and 397.37 are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate, respectively; L is the labeled quantity, in mg, of codeine phosphate hemihydrate in each Tablet; CC is the concentration, in mg per mL, of USP Codeine Phosphate RS in the Standard preparation; CU is the concentration, in mg per mL, of codeine phosphate hemihydrate in the Assay preparation, based upon the labeled quantity per Tablet and the extent of dilution; and the other terms are as defined herein.
Auxiliary Information— Staff Liaison : Clydewyn M. Anthony, Ph.D., Scientist
Expert Committee : (MDCCA05) Monograph Development-Cough Cold and Analgesics
USP29–NF24 Page 40
Pharmacopeial Forum : Volume No. 29(3) Page 602
Phone Number : 1-301-816-8139