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 time of the pseudoephedrine peak in the chromatogram of the Assay preparationrelative to that of the dextromethorphan peak corresponds to that in the chromatogram of the Standard preparationas obtained in the Assay for pseudoephedrine hydrochloride.

Procedure for content uniformity of pseudoephedrine hydrochloride— Proceed as directed in the Assay for pseudoephedrine hydrochloride,preparing the Assay preparationas follows.Transfer 1Capsule to a 100-mLvolumetric flask,add about 50mLof water,heat on a steam bath for about 5minutes,and allow to cool.Add 5.0mLof Internal standard solution,dilute with water to volume,and mix.

Mobile phase— Prepare a mixture of water,methanol,and glacial acetic acid (60:40:1.5).Make any necessary adjustments (see System Suitabilityunder Chromatography á621ñ).

Internal standard solution— Prepare a solution of benzoic acid in methanol containing about 2mg per mL.

Standard stock solution— Prepare a solution in water having known concentrations of about 20mg of USP Guaifenesin RSand 20Jmg of USP Pseudoephedrine Hydrochloride RSper mL,Jbeing the ratio of the labeled amount,in mg,of pseudoephedrine hydrochloride to the labeled amount,in mg,of guaifenesin per Capsule.

Standard preparation— Transfer 10.0mLof the Standard stock solutionto a 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 5.0mLof this solution and 5.0mLof Internal standard solutionto a second 100-mLvolumetric flask,add about 40mLof methanol,dilute with water to volume,and mix.Each mLof this solution contains about 0.1mg of USP Guaifenesin RS,0.1Jmg of USP Pseudoephedrine Hydrochloride RS,and 0.1mg of benzoic acid.

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.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.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 276-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 0.65for guaifenesin and 1.0for benzoic acid;the resolution,R,between the guaifenesin peak and the benzoic acid peak is not less than 3.0;the tailing factors for the guaifenesin peak and the benzoic acid peak are not more than 2.5;and the relative standard deviation for replicate injections is not more than 2.5%.

Procedure— [NOTE—Use peak areas where peak responses are indicated.]Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the 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 response to the benzoic acid peak 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 dextromethorphan hydrobromide in methanol containing about 1.2mg per mL.

Standard stock solution— Prepare as directed in the Assay for guaifenesin.

Standard preparation— Transfer 10.0mLof Standard stock solutionand 5.0mLof Internal standard solutionto a 100-mLvolumetric flask,dilute with water to volume,and mix.Each mLof this solution contains about 2mg of USP Guaifenesin RS,2Jmg of USP Pseudoephedrine Hydrochloride RS,and 0.06mg of dextromethorphan hydrobromide.

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 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the relative retention times are about 0.55for pseudoephedrine and 1.0for dextromethorphan;the resolution,R,between the pseudoephedrine peak and the dextromethorphan peak is not less than 1.5;the tailing factors for the pseudoephedrine peak and the dextromethorphan peak are not more than 1.5and 2.5,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 dextromethorphan peak area response obtained from the Assay preparationand the Standard preparation,respectively.