A: The retention time of the guaifenesin peak relative to that of the benzoic acid peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparationas obtained in the Assay for guaifenesin.

B: The retention times of the pseudoephedrine and dextromethorphan peaks in the chromatogram of the Assay preparationrelative to that of the brompheniramine peak correspond to those in the chromatogram of the Standard preparationas obtained in the Assay for pseudoephedrine hydrochloride and dextromethorphan hydrobromide.

Procedure for content uniformity of pseudoephedrine hydrochlorideand dextromethorphan hydrobromide— Proceed as directed in the Assay for pseudoephedrine hydrochloride and dextromethorphan hydrobromide,preparing the Assay preparationas follows.Transfer 1Capsule to a 100-mLvolumetric flask,add about 50mLof water,heat on a steam bath for about 15minutes,and allow to cool.Add 5.0mLof Internal standard solution,dilute with water to volume,and mix.

Mobile phase,Internal standard solution,Standard stock solution,Standard preparation,and Chromatographic system— Proceed as directed in the Assay for guaifenesinunder Guaifenesin and Pseudoephedrine Hydrochloride Capsules.

Assay preparation— Transfer an accurately counted number of Capsules,equivalent to about 2000mg of guaifenesin,to a 100-mLvolumetric flask,add about 50mLof water,and heat on a steam bath for about 15minutes.Allow to cool,dilute with water to volume,and mix (stock solution).Transfer 10.0mLof this stock solution to a second 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 5.0mLof this solution and 5.0mLof Internal standard solutionto a third 100-mLvolumetric flask,add about 40mLof methanol,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 area responses for the major peaks.Calculate the quantity,in mg,of guaifenesin (C10H14O4)in each Capsule taken by the formula: in which Cis the concentration,in mg per mL,of USP Guaifenesin RSin the Standard preparation,Nis the number of Capsules taken,and RUand RSare the ratios of the guaifenesin peak area response to the benzoic acid peak area response obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase— To 3.5g of docusate sodium add 500mLof methanol,350mLof water,145mLof tetrahydrofuran,and 5mLof glacial acetic acid,mix,and pass through a filter having a porosity of 0.5µm or less.Make any necessary adjustments (see System Suitabilityunder Chromatography á621ñ).

Internal standard solution— Prepare a solution of brompheniramine maleate in methanol containing about 0.3mg per mL.

Standard stock solution— Prepare a solution in water having known concentrations of about 20mg of USP Guaifenesin RS,20Jmg of USP Pseudoephedrine Hydrochloride RSper mL,and 20J¢mg of USP Dextromethorphan Hydrobromide RSper mL,Jbeing the ratio of the labeled amount,in mg,of pseudoephedrine hydrochloride to the labeled amount,in mg,of guaifenesin per Capsule,and J¢being the ratio of the labeled amount,in mg,of dextromethorphan hydrobromide to the labeled amount,in mg,of guaifenesin per Capsule.

Standard preparation— Transfer 10.0mLof Standard stock solutionand 5.0mLof Internal standard solutionto a 100-mLvolumetric flask,dilute with water to volume,and mix.

Assay preparation— Transfer 10.0mLof the stock solution used to prepare the Assay preparationin the Assay for guaifenesinand 5.0mLof Internal standard solutionto a 100-mLvolumetric flask,dilute with water to volume,and mix.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 263-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the relative retention times are about 0.4for pseudoephedrine,0.75for dextromethorphan,and 1.0for brompheniramine;the resolution,R,between the peaks is not less than 1.5;the tailing factors for the pseudoephedrine peak,the dextromethorphan peak,and the brompheniramine peak are not more than 1.5,2.5,and 3.0,respectively;and the relative standard deviation for replicate injections determined for the pseudoephedrine peak is not more than 2.0%.

Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the area responses for the major peaks.Calculate the quantity,in mg,of pseudoephedrine hydrochloride (C10H15NO·HCl)in each Capsule taken by the formula: in which Cis the concentration,in mg per mL,of USP Pseudoephedrine Hydrochloride RSin the Standard preparation,Nis the number of Capsules taken,and RUand RSare the ratios of the pseudoephedrine peak area response to the brompheniramine peak area response obtained from the Assay preparationand the Standard preparation,respectively.Calculate the quantity,in mg,of dextromethorphan hydrobromide (C18H25NO·HBr·H2O)in each Capsule taken by the formula: in which 370.33and 352.31are the molecular weights of dextromethorphan hydrobromide and anhydrous dextromethorphan hydrobromide,respectively;Cis the concentration,in mg per mL,of USP Dextromethorphan Hydrobromide RSin the Standard preparation;Nis the number of Capsules taken;and RUand RSare the ratios of the dextromethorphan peak area response to the brompheniramine peak response obtained from the Assay preparationand the Standard preparation,respectively.