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 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.

Change to read:

for oral powder packaged in single-unit containers: meets the requirements.USP28

Mobile phaseand 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 Hydrochloride 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,dilute with 0.1%phosphoric acid to volume,and mix.

System suitability solution 1 (for Oral Powder that contains 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 Oral Powder that contains no chlorpheniramine salt)— Mix equal volumes of the Standard preparationand the Dextromethorphan standard preparation.

Assay preparation— Transfer the contents of 10unit-dose containers of the Oral Powder to a 2000-mLvolumetric flask.Add 1000mLof water and 2.0mLof phosphoric acid.Gently heat to about 60until the powder is fully dispersed.Cool the flask to room temperature,add 40mLof methanol,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 0.24mg 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 each unit-dose container of Oral Powder 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 unit-dose container;Dis the concentration,in mg per mL,of pseudoephedrine hydrochloride in each mLof the Assay preparation,based on the number of unit-dose containers taken,the labeled quantity,in mg,of pseudoephedrine hydrochloride in each unit-dose container,and the extent of dilution;and rUand rSare the pseudoephedrine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phaseand 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 6.0mg per mL.Transfer 2.0mLof this solution to a 25-mLvolumetric flask,dilute with 0.1%phosphoric acid to volume,and mix.

System suitability solution 1 (for Oral Powder that contains 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 Oral Powder that contains no chlorpheniramine salt)—Mix equal volumes of the Standard preparationand the Dextromethorphan standard preparation.

Assay preparation— Proceed as directed for the Assay preparationin the Assay for pseudoephedrine hydrochlorideto obtain a solution having a concentration of about 0.48mg 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 unit-dose container of Oral Powder taken by the formula: in which the terms are as defined therein,pseudoephedrine sulfate being substituted for pseudoephedrine hydrochloride.

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.

Assay preparation— Transfer the contents of 10unit-dose containers of the Oral Powder to a 2000-mLvolumetric flask.Add 1000mLof water and 2mLof phosphoric acid.Gently heat to about 60until the powder is fully dispersed.Cool the flask to room temperature,add 40mLof methanol,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 0.50mg of acetaminophen per mL.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparation and 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 unit-dose container of Oral Powder 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 unit-dose container;Dis the concentration,in mg per mL,of acetaminophen in the Assay preparation,based on the number of unit-dose containers taken,the labeled quantity,in mg,of acetaminophen in each unit-dose container,and the extent of dilution;and rUand rSare the acetaminophen peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phaseand 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 the contents of 10unit-dose containers of Oral Powder to a 2000-mLvolumetric flask.Add 1000mLof water and 2mLof phosphoric acid.Gently heat to about 60until the powder is fully dispersed.Cool the flask to room temperature,add 40mLof methanol,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 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 unit-dose container of Oral Powder 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 unit-dose container;Dis the concentration,in mg per mL,of chlorpheniramine maleate in each mLof the Assay preparation,based on the number of unit-dose containers taken,the labeled quantity,in mg,of chlorpheniramine maleate in each unit-dose container,and the extent of dilution;and rUand rSare the chlorpheniramine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phaseand 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 0.8mg per mL.Quantitatively dilute a portion of this solution with 0.1%phosphoric acid to obtain a solution having a known concentration of 0.08mg per mL.

Assay preparation— Transfer the contents of 10unit-dose containers of Oral Powder to a 2000-mLvolumetric flask.Add 1000mLof water and 2mLof phosphoric acid.Gently heat to about 60until the powder is fully dispersed.Cool the flask to room temperature,add 40mLof methanol,dilute with water to volume,and mix.If necessary,quantitatively dilute a portion of this solution with 0.1%phosphoric acid to obtain a solution having a concentration of 0.08mg 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 responses for the dextromethorphan peaks.Calculate the quantity,in mg,of dextromethorphan hydrobromide (C18H25NO·HBr·H2O)in each unit-dose container of Oral Powder 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 unit-dose container;Dis the concentration,in mg per mL,of dextromethorphan hydrobromide in each mLof the Assay preparation,based on the number of unit-dose containers taken,the labeled quantity,in mg,of dextromethorphan hydrobromide in each unit-dose container,and the extent of dilution;and rUand rSare the dextromethorphan peak responses obtained from the Assay preparationand the Standard preparation,respectively.