A: The retention times of the major peaks in the chromatograms of the Assay preparationcorrespond to those in the chromatograms of the Standard preparations,as obtained in the Assay for acetaminophenand the Assay for codeine phosphate,respectively.

B: Transfer a volume of Oral Solution,equivalent to about 12mg of codeine phosphate,to a separator,add 1mLof ammonium hydroxide and 5mLof methylene chloride,shake for 1minute,and allow the layers to separate.Use the clear,lower layer as the test solution.Prepare a Standard solution of USP Acetaminophen RSand USP Codeine Phosphate RSin methanol containing 12mg of each per mL.Apply 10µLof each solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)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 UVlight:the RFvalues of the two principal spots obtained from the test solution correspond to those obtained from the Standard solution.

Add the following:

FOR ORAL SOLUTION PACKAGED IN SINGLE-UNIT CONTAINERS: meets the requirements.USP28

Add the following:

FOR ORAL SOLUTION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.USP28

Mobile phase— Prepare a suitable mixture of water and methanol (7:3),and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve an accurately weighed quantity of USP Acetaminophen RSin Mobile phaseto obtain a solution having a known concentration of about 0.48mg per mL.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 120mg of acetaminophen,to a 250-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Chromatographic system(see Chromatography á621ñ)— 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 2.0mLper 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 1000theoretical 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 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the acetaminophen peaks.Calculate the quantity,in mg,of acetaminophen (C8H9NO2)in each mLof the Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Acetaminophen RSin the Standard preparation;Vis the volume,in mL,of Oral Solution taken;and rUand rSare the peak responses of acetaminophen obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase— Dissolve 4.44g of docusate sodium in 1000mLof 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 Suitabilityunder Chromatography á621ñ).

Solvent mixture— Mix water and methanol (7:3).

Standard preparation— Dissolve an accurately weighed quantity of USP Codeine Phosphate RSin Solvent mixtureto obtain a solution having a known concentration of about 0.12mg per mL.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 12mg of codeine phosphate hemihydrate,to a 100-mLvolumetric flask,dilute with Solvent mixtureto volume,and mix.

Chromatographic system(see Chromatography á621ñ)— 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 1.5mLper 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 1500theoretical 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 10µL)of the Standard preparationand the Assay preparationinto 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 mLof the Oral Solution taken by the formula: in which 406.37and 397.37are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate,respectively;Cis the concentration,in mg per mL,of USP Codeine Phosphate RSin the Standard preparation;Vis the volume,in mL,of Oral Solution taken;and rUand rSare the peak responses of codeine phosphate obtained from the Assay preparationand the Standard preparation,respectively.