Acetaminophen and Codeine Phosphate Oral Suspension
» Acetaminophen and Codeine Phosphate Oral Suspension is a suspension of Acetaminophen and Codeine Phosphate in a suitable aqueous vehicle. It 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
A: The retention times of the major peaks in the chromatograms of the Assay preparations correspond to those in the chromatograms of the Standard preparation, as obtained in the Assay.
B: Using the Oral Suspension, proceed as directed for Identification test B under Acetaminophen and Codeine Phosphate Oral Solution: the indicated results are obtained.
Uniformity of dosage units 905
for oral suspension packaged in single-unit containers: meets the requirements.
Deliverable volume 698
for oral suspension packaged in multiple-unit containers: meets the requirements.
pH 791: between 4.0 and 6.1.
Mobile phase Dissolve 4.9 g of monobasic potassium phosphate in 900 mL of water, adjust with phosphoric acid to a pH of 3.9, add 216 mg of sodium 1-octanesulfonate, and mix. Add 100 mL of acetonitrile, mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent Prepare a mixture of 0.01 N sodium hydroxide and methanol (70:30).
Codeine phosphate standard stock solution Prepare a solution of USP Codeine Phosphate RS, accurately weighed, in Diluent having a known concentration of about 0.5 mg per mL.
Standard stock preparation Transfer an accurately weighed quantity of about 5J mg of USP Acetaminophen RS, J being the ratio of the labeled amount, in mg, of acetaminophen to the labeled amount, in mg, of codeine phosphate hemihydrate, and 10.0 mL of Codeine phosphate standard stock solution to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.
Standard preparation Transfer 10.0 mL of Standard stock preparation to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 0.01 mg of USP Codeine Phosphate RS and 0.01J mg of USP Acetaminophen RS per mL.
Assay preparation Transfer an accurately measured volume of well-mixed Oral Suspension, equivalent to about 50 mg of acetaminophen, to a 100-mL volumetric flask. Add 50 mL of Diluent, and mix by mechanical means for 30 minutes. Dilute with Diluent to volume, and mix. [noteFoaming may be minimized by adding a few drops of acetonitrile before diluting with Diluent to volume. ] Centrifuge a portion of this mixture, and transfer 10.0 mL of the clear supernatant to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Resolution solution Prepare a solution in Diluent containing about 0.02 mg of sodium benzoate and 0.03 mg of methylparaben per mL. Transfer 10.0 mL of this solution and 10.0 mL of Standard stock preparation to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L11. The flow rate is about 2 mL per minute. Chromatograph the Resolution solution, and measure the peak responses as directed for Procedure: the relative retention times are about 0.25 for acetaminophen, 0.5 for benzoate, 1.0 for codeine, and 1.3 for methylparaben; and the resolution, R, between each pair of adjacent peaks is not less than 2. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for each analyte peak is not more than 2, the peak efficiency is not less than 500 theoretical plates, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in each mL of the Oral Suspension taken by the formula:
500(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 Suspension taken; and rU and rS are the acetaminophen 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 each mL of the Oral Suspension taken by the formula:
(406.37/397.37)(500C/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 Suspension taken; and rU and rS are the codeine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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