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 diphenhydramine in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for diphenhydramine hydrochloride.

C: 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.

Medium: pH5.8phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions);900mL.

Apparatus 2: 50rpm.

Time: 45minutes.

Buffer solution,Diluting solvent,Mobile phase,andChromatographic system— Proceed as directed in the Assay for acetaminophen.

Standard solution— Prepare as directed for the Standard preparationin the Assay for acetaminophen.

Test solution 1— Combine equal volumes of the filtered solutions under test,and use the pooled sample.

Test solution 2— Transfer 5.0mLof Test solution 1to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Procedure— Using Test solution 1and the Standard solution,and making any necessary volumetric adjustments,proceed as directed in the Assay for diphenhydramine hydrochlorideand the Assay for pseudoephedrine hydrochloride,and determine the amounts of diphenhydramine hydrochloride (C17H21NO·HCl)and pseudoephedrine hydrochloride (C10H15NO·HCl)dissolved.Using Test solution 2and the Standard solution,and making any necessary volumetric adjustments,proceed as directed in the Assay for acetaminophen,and determine the amount of acetaminophen (C8H9NO2)dissolved.

Tolerances— Not less than 75%(Q)of the labeled amounts of C8H9NO2,C17H21NO·HCl,and C10H15NO·HCl is dissolved in 45minutes.

FOR TABLETS LABELED AS CHEWABLE—

Buffer solution— Transfer 6.8g of monobasic potassium phosphate to a 1000-mLvolumetric flask,and add water to dissolve.Add 2.0mLof triethylamine,dilute with water to volume,and mix.Adjust with phosphoric acid to a pHof 4.0.

Diluting solvent— Prepare a mixture of Buffer solutionand acetonitrile (89:11).

Mobile phase— Prepare a filtered and degassed mixture of Buffer solutionand acetonitrile (94:6).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve accurately weighed quantities of USP Acetaminophen RS,USP Diphenhydramine Hydrochloride RS,and USP Pseudoephedrine Hydrochloride RSin Diluting solvent,and dilute quantitatively,and stepwise if necessary,with Diluting solventto obtain a solution having known concentrations of about 0.025mg per mL,0.0125mg per mL,and 0.03mg per mL,respectively.

Assay preparation— Weigh and finely powder not fewer than 20Tablets,and transfer an accurately weighed portion of the powder,equivalent to about 500mg of acetaminophen,to a 100-mLvolumetric flask.Add about 75mLof Diluting solvent,shake,and sonicate for 15minutes.Cool to room temperature,dilute with Diluting solventto volume,and mix.Dilute an accurately measured volume of the solution quantitatively,and stepwise if necessary,with Diluting solventto obtain a solution having a concentration of about 25µg of acetaminophen per mL.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×15-cm column that contains packing L10.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiencies,determined from the acetaminophen,diphenhydramine,and pseudoephedrine peaks,are not less than 3000theoretical plates;the tailing factors for the acetaminophen,diphenhydramine,and pseudoephedrine peaks are not more than 2.0;and the relative standard deviations determined from the acetaminophen,diphenhydramine hydrochloride,and pseudoephedrine hydrochloride responses for replicate injections are not more 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 acetaminophen peak responses.Calculate the quantity,in mg,of acetaminophen (C8H9NO2)in the portion of Tablets taken by the formula: in which Cis the concentration,in µg per mL,of USP Acetaminophen RSin the Standard preparation;and rUand rSare the acetaminophen peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Buffer solution,Diluting solvent,Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assay for acetaminophen.

Assay preparation— Weigh and finely powder not fewer than 20Tablets,and transfer an accurately weighed portion of the powder,equivalent to about 12.5mg of diphenhydramine hydrochloride,to a 100-mLvolumetric flask.Add about 75mLof Diluting solvent,shake,and sonicate for 15minutes.Cool to room temperature,dilute with Diluting solventto volume,and mix.Dilute an accurately measured volume of this solution quantitatively,and stepwise if necessary,with Diluting solventto obtain a solution having a concentration of about 12.5µg of diphenhydramine per mL.

Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the diphenhydramine peak responses.Calculate the quantity,in mg,of diphenhydramine hydrochloride (C17H21NO·HCl)in the portion of Tablets taken by the formula: in which Cis the concentration,in mg per mL,of USP Diphenhydramine Hydrochloride RSin the Standard preparation;and rUand rSare the diphenhydramine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Buffer solution,Diluting solvent,Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assay for acetaminophen.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 30mg of pseudoephedrine hydrochloride,to a 100-mLvolumetric flask,add about 75mLof Diluting solvent,shake,and sonicate for 15minutes.Cool to room temperature,dilute with Diluting solventto volume,and mix.Dilute an accurately measured volume of this solution quantitatively,and stepwise if necessary,with Diluting solventto obtain a solution having a concentration of about 30µg of pseudoephedrine hydrochloride per mL.

Procedure— Separately inject equal volumes (about 20µL)of the Assay preparationand the Standard preparationinto the chromatograph,record the chromatograms,and measure the pseudoephedrine peak responses.Calculate the quantity,in mg per mL,of pseudoephedrine hydrochloride (C10H15NO·HCl)in the portion of Tablets taken by the formula: in which Cis the concentration,in mg per mL,of USP Pseudoephedrine Hydrochloride RSin the Standard preparation;and rUand rSare the pseudoephedrine peak responses obtained from the Assay preparationand the Standard preparation,respectively.