Acetaminophen and Codeine Phosphate Oral Solution
» Acetaminophen and Codeine Phosphate Oral Solution contains not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of acetaminophen (C8H9NO2) and codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O).
Packaging and storage— Preserve in tight, light-resistant containers, and store at controlled room temperature.
USP Reference standards 11
USP Acetaminophen RS Click to View Structure
USP Codeine Phosphate RS Click to View Structure
Identification—
A: The retention times of the major peaks in the chromatograms of the Assay preparation correspond to those in the chromatograms of the Standard preparations, as obtained in the Assay for acetaminophen and the Assay for codeine phosphate, respectively.
B: Transfer a volume of Oral Solution, equivalent to about 12 mg of codeine phosphate, to a separator, add 1 mL of ammonium hydroxide and 5 mL of methylene chloride, shake for 1 minute, and allow the layers to separate. Use the clear, lower layer as the test solution. Prepare a Standard solution of USP Acetaminophen RS and USP Codeine Phosphate RS in methanol containing 12 mg of each per mL. Apply 10 µL of each solution to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of methanol and ammonium hydroxide (49:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate. Locate the spots on the plate by examination under short-wavelength UV light: the RF values of the two principal spots obtained from the test solution correspond to those obtained from the Standard solution.
Uniformity of dosage units 905
for oral solution packaged in single-unit containers: meets the requirements.
Deliverable volume 698
for oral solution packaged in multiple-unit containers: meets the requirements.
pH 791: between 4.0 and 6.1.
Alcohol content (if present), Method II 611: between 90.0% and 120.0% of the labeled amount of C2H5OH, acetone being used as the internal standard.
Assay for acetaminophen—
Mobile phase— Prepare a suitable mixture of water and methanol (7:3), and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Acetaminophen RS in Mobile phase to obtain a solution having a known concentration of about 0.48 mg per mL.
Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 120 mg of acetaminophen, to a 250-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency determined from the analyte peak is not less than 1000 theoretical plates, the tailing factor for the analyte peak is not more than 1.5, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the acetaminophen peaks. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in each mL of the Oral Solution taken by the formula:
250(C/V)(rU / rS)
in which C is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; V is the volume, in mL, of Oral Solution taken; and rU and rS are the peak responses of acetaminophen obtained from the Assay preparation and the Standard preparation, respectively.
Assay for codeine phosphate—
Mobile phase— Dissolve 4.44 g of docusate sodium in 1000 mL of a mixture of methanol, water, tetrahydrofuran, and phosphoric acid (600:360:40:1) with stirring, and pass through a membrane filter having a 0.45-µm or finer porosity. Make adjustments if necessary (see System Suitability under Chromatography 621).
Solvent mixture— Mix water and methanol (7:3).
Standard preparation— Dissolve an accurately weighed quantity of USP Codeine Phosphate RS in Solvent mixture to obtain a solution having a known concentration of about 0.12 mg per mL.
Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 12 mg of codeine phosphate hemihydrate, to a 100-mL volumetric flask, dilute with Solvent mixture to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 30-cm column that contains 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 column efficiency determined from the analyte peak is not less than 1500 theoretical plates; the tailing factor for the analyte peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 3.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the codeine peaks. Calculate the quantity, in mg, of codeine phosphate hemihydrate (C18H21NO3·H3PO4·½H2O) in each mL of the Oral Solution taken by the formula:
(406.37/397.37)(100C/V)(rU / rS)
in which 406.37 and 397.37 are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate, respectively; C is the concentration, in mg per mL, of USP Codeine Phosphate RS in the Standard preparation; V is the volume, in mL, of Oral Solution taken; and rU and rS are the peak responses of codeine phosphate obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison
1-301-816-8139
(SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 2053
Pharmacopeial Forum: Volume No. 30(1) Page 46