A: The retention time of the major peak for acetaminophen in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for acetaminophen.

B: The retention time of the major peak for dextromethorphan in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for dextromethorphan hydrobromide.

C: The retention time of the major peak for doxylamine in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for doxylamine succinate.

D: The retention time of the major peak for pseudoephedrine in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for pseudoephedrine hydrochloride.

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 filtered and degassed mixture of water and methanol (55:45).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve an accurately weighed quantity of USP Acetaminophen RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 0.2mg per mL.

Assay preparation— Dissolve an accurately measured volume of Oral Solution,equivalent to about 200mg of acetaminophen,in Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a concentration of about 0.2mg of acetaminophen per mL.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 1mLper 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 500theoretical plates;the tailing factor for the acetaminophen peak is not greater than 2.0;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;Lis the labeled quantity,in mg per mL,of acetaminophen in the Oral Solution;Dis the concentration,in mg per mL,of acetaminophen in the Assay preparation;and rUand rSare the acetaminophen peak responses obtained from the Assay preparationand the Standard preparation,respectively.

0.05M Buffer solution— Dissolve 6.8g of monobasic potassium phosphate in 1Lof water.

Mobile phase— Prepare a filtered and degassed mixture of 0.05M Buffer solutionand acetonitrile (55:45).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve accurately weighed quantities of USP Dextromethorphan Hydrobromide RS,USP Doxylamine Succinate RS,and USP Pseudoephedrine Hydrochloride RSin Mobile phase,and,dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having known concentrations of about 0.1,0.04,and 0.2mg per mL,respectively.

Assay preparation— Dissolve an accurately measured volume of Oral Solution,equivalent to about 5mg of dextromethorphan hydrobromide,in Mobile phase,and quantitatively dilute with Mobile phaseto obtain a solution having a concentration of about 0.1mg per mL.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×25-cm column that contains packing L9.The flow rate is about 2.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.38for pseudoephedrine,0.65for dextromethorphan,and 1.0for doxylamine;the tailing factors for the dextromethorphan,doxylamine,and pseudoephedrine peaks are not more than 2.5;the column efficiencies for the dextromethorphan,doxylamine,and pseudoephedrine peaks are not less than 500;and the relative standard deviations of the dextromethorphan,doxylamine,and pseudoephedrine responses for replicate injections are 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 dextromethorphan peak responses.Calculate the quantity,in mg per mL,of dextromethorphan hydrobromide (C18H25NO·HBr·H2O)in the portion of Oral Solution taken by the formula: in which 370.33and 352.32are the molecular weights of dextromethorphan hydrobromide monohydrate and anhydrous dextromethorphan hydrobromide,respectively;Cis the concentration,in mg per mL,of USP Dextromethorphan Hydrobromide RSin the Standard preparation;Lis the labeled quantity,in mg per mL,of dextromethorphan hydrobromide in the Oral Solution;Dis the concentration,in mg per mL,of dextromethorphan hydrobromide in the Assay preparation;and rUand rSare the dextromethorphan peak responses obtained from the Assay preparationand the Standard preparation,respectively.

0.05M Buffer solution,Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assay for dextromethorphan hydrobromide.

Assay preparation— Dissolve an accurately measured volume of Oral Solution,equivalent to about 2mg of doxylamine succinate,in Mobile phase,and dilute with Mobile phaseto obtain a solution having a concentration of about 0.04mg per mL.

Procedure— Proceed as directed for Procedurein the Assay for dextromethorphan hydrobromide.Calculate the quantity,in mg per mL,of doxylamine succinate (C17H22N2O·C4H6O4)in the portion of Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Doxylamine Succinate RSin the Standard preparation;Lis the labeled quantity,in mg per mL,of doxylamine succinate in the Oral Solution;Dis the concentration,in mg per mL,of doxylamine succinate in the Assay preparation;and rUand rSare the doxylamine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

0.05M Buffer solution,Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assay for dextromethorphan hydrobromide.

Assay preparation— Dissolve an accurately measured volume of Oral Solution,equivalent to about 10mg of pseudoephedrine hydrochloride,in Mobile phase,and dilute with Mobile phaseto obtain a solution having a concentration of about 0.2mg per mL.

Procedure— Proceed as directed for Procedurein the Assay for dextromethorphan hydrobromide.Calculate the quantity,in mg per mL,of pseudoephedrine hydrochloride (C10H15NO·HCl)in the portion of Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Pseudoephedrine Hydrochloride RSin the Standard preparation;Lis the labeled amount,in mg per mL,of pseudoephedrine hydrochloride in the Oral Solution;Dis the concentration,in mg per mL,of pseudoephedrine hydrochloride in the Assay preparation;and rUand rSare the pseudoephedrine peak responses obtained from the Assay preparationand the Standard preparation,respectively.