A: If phenylpropanolamine hydrochloride is claimed in the labeling to be present,the chromatogram of the Assay preparation,obtained as directed in the Assay for phenylpropanolamine hydrochloride,exhibits a major peak for phenylpropanolamine,the retention time of which corresponds to that exhibited by the Standard preparation.

B: If acetaminophen is claimed in the labeling to be present,the chromatogram of the Assay preparation,obtained as directed in the Assay for acetaminophen,exhibits a major peak for acetaminophen,the retention time of which corresponds to that exhibited by the Standard preparation.

C: If chlorpheniramine maleate is claimed in the labeling to be present,the chromatogram of the Assay preparation,obtained as directed in the Assay for chlorpheniramine maleate,exhibits a major peak for chlorpheniramine,the retention time of which corresponds to that exhibited by the Standard preparation.

D: If dextromethorphan hydrobromide is claimed in the labeling to be present,the chromatogram of the Assay preparation,obtained as directed in the Assay for dextromethorphan hydrobromide,exhibits a major peak for dextromethorphan,the retention time of which corresponds to that exhibited by the Standard preparation.

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 (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve an accurately weighed quantity of USP Phenylpropanolamine Hydrochloride RSin water to obtain a solution having a known concentration of about 0.5mg per mL.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,add 8.0mLof Mobile phase,dilute with water to volume,and mix.

Chlorpheniramine standard preparation— Prepare as directed for Standard preparationin the Assay for chlorpheniramine maleate.

Dextromethorphan standard preparation— Prepare as directed for Standard preparationin the Assay for dextromethorphan hydrobromide.

System suitability solution 1 (for Oral Solution that contains either all the four ingredients or a combination of three containing chlorpheniramine salt)—Mix equal volumes of the Standard preparationand the Chlorpheniramine standard preparation.

System suitability solution 2 (for Oral Solution that contains no chlorpheniramine salt)—Mix equal volumes of the Standard preparationand the Dextromethorphan standard preparation.

Assay preparation— Transfer an accurately measured volume of the Oral Solution,equivalent to 2.5mg of phenylpropanolamine hydrochloride,to a 50-mLvolumetric flask,add about 40mLof Mobile 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 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor for the phenylpropanolamine peak is not greater than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.Separately inject about 10µLof System suitability solution 1or System suitability solution 2,as appropriate.The resolution,R,between phenylpropanolamine and chlorpheniramine or between phenylpropanolamine and dextromethorphan is not less than 2.0.

Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the phenylpropanolamine peaks.Calculate the quantity,in mg per mL,of phenylpropanolamine hydrochloride (C9H13NO·HCl),in the volume of Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Phenylpropanolamine Hydrochloride RSin the Standard preparation;Vis the volume,in mL,of the Oral Solution taken;and rUand rSare the phenylpropanolamine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase— Prepare a suitable degassed and filtered mixture of water,methanol,and glacial acetic acid (79:20:1).Make any necessary adjustments (see System Suitabilityunder Chromatography 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 the Standard preparation,and record the peak responses as directed for Procedure: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 5µL)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 per mL,of acetaminophen (C8H9NO2)in the volume of 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 the Oral Solution taken;and rUand rSare the acetaminophen peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase and Chromatographic system—Proceed as directed in the Assay for phenylpropanolamine hydrochloride.

Standard preparation— Dissolve an accurately weighed quantity of USP Chlorpheniramine Maleate RSin water to obtain a solution having a known concentration of about 0.08mg per mL.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,add 8mLof Mobile phase,dilute with water to volume,and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 0.4mg of chlorpheniramine maleate,to a 50-mLvolumetric flask.Add 40mLof Mobile phase,dilute with water to volume,and mix.

Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the chlorpheniramine peaks.Calculate the quantity,in mg per mL,of chlorpheniramine maleate (C16H19ClN2·C4H4O4)in the volume of Oral Solution taken by the formula: in which Cis the concentration,in mg per mL,of USP Chlorpheniramine Maleate RSin the Standard preparation;Vis the volume,in mL,of the Oral Solution taken;and rUand rSare the chlorpheniramine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase andChromatographic system— Proceed as directed in the Assay for phenylpropanolamine hydrochloride.

Standard preparation— Dissolve an accurately weighed quantity of USP Dextromethorphan Hydrobromide RSin water to obtain a solution having a known concentration of about 0.4mg per mL.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,add 8mLof Mobile phase,dilute with water to volume,and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution,equivalent to about 2mg of dextromethorphan hydrobromide,to a 50-mLvolumetric flask,add 40mLof Mobile phase,dilute with water to volume,and mix.

Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the dextromethorphan peaks.Calculate the quantity,in mg per mL,of dextromethorphan hydrobromide (C18H25NO·HBr ·H2O)in the volume 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;Vis the volume,in mL,of Oral Solution taken;and rUand rSare the dextromethorphan peak responses obtained from the Assay preparationand the Standard preparation,respectively.