A: If pseudoephedrine hydrochloride or pseudoephedrine sulfate is purported 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 preparation corresponds 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 dextromethorphan in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for dextromethorphan hydrobromide.

Medium: water;900mL.

Apparatus 1: 100rpm.

Time: 45minutes.

Test preparation— Mix 9.0mLof a filtered portion of the solution under test with 1.0mLof 1%phosphoric acid solution.

Procedure— Determine the amounts of pseudoephedrine hydrochloride or pseudoephedrine sulfate (as appropriate),acetaminophen,chlorpheniramine maleate,and dextromethorphan hydrobromide dissolved,employing the procedures set forth in the Assay for pseudoephedrine hydrochlorideor Assay for pseudoephedrine sulfate,Assay for acetaminophen,Assay for chlorpheniramine maleate,and Assay for dextromethorphan hydrobromide,respectively,making any necessary volumetric adjustments.

Tolerances— Not less than 75%(Q)of the labeled amounts of pseudoephedrine hydrochloride (C10H15NO·HCl)or pseudoephedrine sulfate [(C10H15NO)2·H2SO4],acetaminophen (C8H9NO2),chlorpheniramine maleate (C16H19ClN2·C4H4O4),and dextromethorphan hydrobromide (C18H25NO·HBr·H2O)are dissolved in 45minutes.

Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assay for pseudoephedrine hydrochlorideunder Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine,Dextromethorphan,and Pseudoephedrine.

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 Capsules that contain either all 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 Capsules that contain no chlorpheniramine)—Mix equal volumes of the Standard preparationand the Dextromethorphan standard preparation.

Assay preparation— Transfer not fewer than 10Capsules,accurately counted,to a 500-mLvolumetric flask.Add about 100mLof water and 10mLof 5%phosphoric acid,and gently heat until the Capsules are fully dispersed.Cool the solution to room temperature,dilute with water to volume,mix,and filter.Quantitatively dilute a portion of this solution,if necessary,with water to obtain a solution having a concentration of about 0.12mg of pseudoephedrine hydrochloride per mL.

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 pseudoephedrine peaks.Calculate the quantity,in mg,of pseudoephedrine hydrochloride (C10H15NO·HCl)in the Capsules taken by the formula: in which Cis the concentration,in mg per mL,of USP Pseudoephedrine Hydrochloride RSin the Standard preparation;Lis the labeled quantity,in mg,of pseudoephedrine hydrochloride in each Capsule;Dis the concentration,in mg per mL,of pseudoephedrine hydrochloride in the Assay preparation,based on the number of Capsules taken,the labeled quantity,in mg,of pseudoephedrine hydrochloride in each Capsule and the extent of dilution;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 the Assay for pseudoephedrine hydrochlorideunder Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine,Dextromethorphan,and Pseudoephedrine.

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.

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 2.0mLof this solution to a 25-mLvolumetric flask,add 2.5mLof methanol,dilute with 0.1%phosphoric acid to volume,and mix.

Assay preparation— Proceed as directed for the Assay preparationin the Assay for pseudoephedrine hydrochlorideto obtain a solution having a concentration of about 0.24mg of pseudoephedrine sulfate per mL.

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

Mobile phase— Prepare a filtered and degassed mixture of water,methanol,and glacial acetic acid (79:20:1).Make adjustments,if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Transfer about 25mg of USP Acetaminophen RS,accurately weighed,to a 100-mLvolumetric flask.Add 4mLof methanol,and mix until solution is complete.Add 0.2mLof phosphoric acid,dilute with water to volume,and mix to obtain a solution having a known concentration of about 0.25mg per mL.

Assay preparation— Transfer not fewer than 10Capsules,accurately counted,to a 500-mLvolumetric flask.Add about 100mLof water and 10mLof 5%phosphoric acid,and gently heat until the Capsules are fully dispersed.Cool the solution to room temperature,dilute with water to volume,and mix.Quantitatively dilute a portion of this solution,if necessary,with 0.1%phosphoric acid to obtain a solution having a concentration of about 0.25mg of acetaminophen per mL.

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 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 Capsule 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,of acetaminophen in each Capsule;Dis the concentration,in mg per mL,of acetaminophen in each mLof the Assay preparation,based on the number of Capsules taken,the labeled quantity,in mg,of acetaminophen in each Capsule,and the extent of dilution;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 pseudoephedrine hydrochlorideunder Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine,Dextromethorphan,and Pseudoephedrine.

Standard preparation— Dissolve an accurately weighed quantity of USP Chlorpheniramine Maleate RSin water to obtain a solution having a known concentration of about 0.8mg per mL.Quantitatively dilute a portion of this solution with 0.1%phosphoric acid to obtain a solution having a known concentration of about 8µg per mL.

Assay preparation— Transfer not fewer than 10Capsules,accurately counted,to a 500-mLvolumetric flask.Add about 100mLof water and 10mLof 5%phosphoric acid,and gently heat until the Capsules are fully dispersed.Cool the solution to room temperature,dilute with water to volume,mix,and filter.Quantitatively dilute a portion of this solution,if necessary,with 0.1%phosphoric acid to obtain a solution having a concentration of about 8µg of chlorpheniramine maleate per mL.

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 chlorpheniramine peaks.Calculate the quantity,in mg,of chlorpheniramine maleate (C16H19ClN2·C4H4O4)in each Capsule taken by the formula: in which Cis the concentration,in mg per mL,of USP Chlorpheniramine Maleate RSin the Standard preparation;Lis the labeled quantity,in mg,of chlorpheniramine maleate in each Capsule;Dis the concentration,in mg per mL,of chlorpheniramine maleate in each mLof the Assay preparation,based on the number of Capsules taken,the labeled quantity,in mg,of chlorpheniramine maleate in each Capsule,and the extent of dilution;and rUand rSare the chlorpheniramine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase and Chromatographic system— Proceed as directed in the Assay for pseudoephedrine hydrochlorideunder Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine,Dextromethorphan,and Pseudoephedrine.

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.Quantitatively dilute a portion of this solution with 0.1%phosphoric acid to obtain a solution having a known concentration of about 0.04mg per mL.

Assay preparation— Transfer not fewer than 10Capsules,accurately counted,to a 500-mLvolumetric flask.Add about 100mLof water and 10mLof 5%phosphoric acid,and gently heat until the Capsules are fully dispersed.Cool the solution to room temperature,dilute with water to volume,mix,and filter.Quantitatively dilute a portion of this solution,if necessary,with 0.1%phosphoric acid to obtain a solution having a concentration of about 0.04mg of dextromethorphan hydrobromide per mL.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the peak responses for the dextromethorphan peaks.Calculate the quantity,in mg,of dextromethorphan hydrobromide (C18H25NO·HBr·H2O)in each Capsule 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,of dextromethorphan hydrobromide in each Capsule;Dis the concentration,in mg per mL,of dextromethorphan hydrobromide in each mLof the Assay preparation,based on the number of Capsules taken,the labeled quantity,in mg,of dextromethorphan hydrobromide in each Capsule,and the extent of dilution;and rUand rSare the dextromethorphan peak responses obtained from the Assay preparationand the Standard preparation,respectively.