A: If pseudoephedrine hydrochloride or pseudoephedrine sulfate is claimed in the labeling to be present,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 hydrochlorideor the Assay for pseudoephedrine sulfate.

B: If acetaminophen is claimed in the labeling to be present,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.

C: If chlorpheniramine maleate is claimed in the labeling to be present,the retention time of the major peak for chlorpheniramine in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for chlorpheniramine maleate.

D: If dextromethorphan hydrobromide is claimed in the labeling to be present,the retention time of the major peak for dextromethorphanin the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for dextromethorphan hydrobromide.

Add the following:

For Oral Solution Packaged In Single-Unit Containers: meets the requirements.

Add the following:

For Oral Solution Packaged In Multiple-Unit Containers: meets the requirements.USP28

Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40)containing 0.34g of monobasic potassium phosphate,0.15g of triethylamine hydrochloride,0.25g of sodium lauryl sulfate,and 0.1mLof phosphoric acid in each 100mLof solution.Make adjustments if necessary (seeSystem Suitability underChromatography á621ñ).

Standard preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RSin water to obtain a solution having a known concentration of about 1.5mg per mL.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,add 8.0mLofMobile phase,dilute with water to volume,and mix.

Chlorpheniramine standard preparation— Prepare as directed forStandard preparation in theAssay for chlorpheniramine maleate.

Dextromethorphan standard preparation— Prepare as directed forStandard preparation in theAssay for dextromethorphan hydrobromide.

System suitability solution 1(for Oral Powder that contains either all the four ingredients or a combination of three containing chlorpheniramine salt)— Mix equal volumes of theStandard preparation and theChlorpheniramine standard preparation.

System suitability solution 2(for Oral Powder that contains no chlorpheniramine salt)— Mix equal volumes of theStandard preparation and theDextromethorphan standard preparation.

Assay preparation— Transfer an accurately measured volume of the Oral Solution,equivalent to 15mg of pseudoephedrine hydrochloride,to a 100-mLvolumetric flask,add 80.0mLofMobile phase,dilute with water to volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm ×15-cm column that contains packing L11.The flow rate is about 2mLper minute.Chromatograph theStandard preparation,and record the peak responses as directed forProcedure:the tailing factor for the pseudoephedrine peak is not greater than 2.5;and the relative standard deviation for replicate injections is not more than 2.0%.Separately inject about 10µLofSystem suitability solution 1orSystem suitability solution 2,as appropriate.The resolution,R,between pseudoephedrine and chlorpheniramine or between pseudoephedrine and dextromethorphan is not less than 2.0.

Procedure— Separately inject equal volumes (about 10µL)of theStandard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the responses for the pseudoephedrine peaks.Calculate the quantity,in mg,of pseudoephedrine hydrochloride (C10H15NO·HCl)in each mLof the Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Pseudoephedrine Hydrochloride RSin theStandard preparation;Vis the volume,in mL,of the Oral Solution taken;and rUand rSare the pseudoephedrine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase,System suitability solutions,and Chromatographic system— Proceed as directed in theAssay for pseudoephedrine hydrochloride.

Chlorpheniramine standard preparation— Prepare as directed forStandard preparation in theAssay for chlorpheniramine maleate.

Dextromethorphan standard preparation— Prepare as directed forStandard preparation in theAssay for dextromethorphan hydrobromide.

Standard preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Sulfate RSin water to obtain a solution having a known concentration of about 3.0mg per mL.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,add 4.0mLofMobile phase,dilute with water to volume,and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to 30mg of pseudoephedrine sulfate,to a 100-mLvolumetric flask,add 80.0mLofMobile phase,dilute with water to volume,and mix.

Procedure— Proceed as directed forProcedure in theAssay for pseudoephedrine hydrochloride.Calculate the quantity,in mg,of pseudoephedrine sulfate [(C10H15NO)2·H2SO4]in each mLof the Oral Solution taken by the formula: in which the terms are as defined therein,pseudoephedrine sulfate being substituted for pseudoephedrine hydrochloride.

Mobile phase— Prepare a suitable degassed and filtered mixture of water,methanol,and glacial acetic acid (79:20:1).Make any necessary adjustments (seeSystem Suitability underChromatography á621ñ).

Standard preparation— Transfer about 16.5mg of USP Acetaminophen RS,accurately weighed,to a 100-mLvolumetric flask.Add 2.5mLof methanol,and mix until solution is complete.Dilute with water to volume,and mix to obtain a solution having a known concentration of about 0.165mg per mL.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 33mg of acetaminophen,to a 200-mLvolumetric flask,add 5mLof methanol,and mix.Dilute with water to volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm ×15-cm column that contains packing L7.The flow rate is about 1mLper minute.Chromatograph theStandard preparation,and record the peak responses as directed forProcedure: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 theStandard preparation and theAssay 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 mLof the Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Acetaminophen RSin theStandard preparation;Vis the volume,in mL,of the Oral Solution taken;and rUand rSare the acetaminophen peak responses obtained from theAssay preparation and theStandard preparation,respectively.

Mobile phaseand Chromatographic system— Proceed as directed in theAssay for pseudoephedrine hydrochloride.

Standard preparation— Dissolve an accurately weighed quantity of USP Chlorpheniramine Maleate RSin water to obtain a solution having a known concentration of about 1mg per mL.Transfer 1.0mLof this solution to a 100-mLvolumetric flask,add 80mLofMobile phase,dilute with water to volume,and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 1mg of chlorpheniramine maleate,to a 100-mLvolumetric flask.Add 80mLofMobile phase,dilute with water to volume,and mix.

Procedure— Separately inject equal volumes (about 10µL)of theStandard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the responses for the chlorpheniramine peaks.Calculate the quantity,in mg,of chlorpheniramine maleate (C16H19ClN2·C4H4O4)in the Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Chlorpheniramine Maleate RSin theStandard preparation;Vis the volume,in mL,of the Oral Solution taken;and rUand rSare the chlorpheniramine peak responses obtained from theAssay preparation and theStandard preparation,respectively.

Mobile phaseand Chromatographic system— Proceed as directed in theAssay for pseudoephedrine hydrochloride.

Standard preparation— Dissolve an accurately weighed quantity of USP Dextromethorphan Hydrobromide RSin water to obtain a solution having a known concentration of about 1.5mg per mL.Transfer 5.0mLof this solution to a 100-mLvolumetric flask,add 80mLofMobile phase,dilute with water to volume,and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 7.5mg of dextromethorphan hydrobromide,to a 100-mLvolumetric flask,add 80mLofMobile phase,dilute with water to volume,and mix.

Procedure— Separately inject equal volumes (about 10µL)of theStandard preparation and theAssay preparation into the chromatograph,record the chromatograms,and measure the responses for the dextromethorphan peaks.Calculate the quantity,in mg,of dextromethorphan hydrobromide (C18H25NO·HBr·H2O)in each mLof the 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 theStandard preparation;Vis the volume,in mL,of the Oral Solution taken;and rUand rSare the dextromethorphan peak responses obtained from theAssay preparation and theStandard preparation,respectively.