A: The retention time of the major peak for chlorpheniramine maleate in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for chlorpheniramine maleate.

B: The retention time of the major peak for pseudoephedrine hydrochloride in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay for pseudoephedrine hydrochloride.

Test 1: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 1.

Medium: water;900mL.

Apparatus 2: 50rpm.

Times: 3,6,and 12hours.

Procedure— Determine the amounts of chlorpheniramine maleate (C16H19ClN2·C4H4O4)and pseudoephedrine hydrochloride (C10H15NO·HCl)dissolved by employing the methods set forth in the Assay for chlorpheniramine maleateand the Assay for pseudoephedrine hydrochloride,respectively.

Tolerances— The percentages of the labeled amounts of C16H19ClN2·C4H4O4and C10H15NO·HCl dissolved at the specified times conform to Acceptance Table 1.

Test 2: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 2.

Medium 1: simulated gastric fluid TS,prepared without pepsin;900mL.

Medium 2: simulated intestinal fluid TS,prepared without pancreatin;900mL.

Apparatus 2: 50rpm.

Time for Medium 1: 1.5hours.

Times for Medium 2: 3and 6hours.

Procedure— Determine the amounts of chlorpheniramine maleate (C16N19ClN2·C4H4O4)and pseudoephedrine hydrochloride (C10H15NO·HCl)dissolved by employing the methods set forth in the Assay for chlorpheniramine maleateand the Assay for pseudoephedrine hydrochloride,respectively,using Standard solutions having known concentrations of the relevant USP Reference Standard in the appropriate Medium.

Tolerances— The percentages of the labeled amounts of C16N19ClN2·C4H4O4and C10H15NO·HCl dissolved at the specified times conform to Acceptance Table 2.

Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40)containing 0.34g of monobasic potassium phosphate,0.15g of triethylamine hydrochloride,0.25g of sodium lauryl sulfate,and 0.1mLof phosphoric acid in each 100mLof solution.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

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 a phosphoric acid solution (1in 1000)to obtain a solution having a known concentration of about 8µg per mL.

Assay preparation— Transfer not fewer than 10Capsules to a suitable container.Add 100mLof water and 10mLof a phosphoric acid solution (1in 20),and heat gently until the Capsules are fully dispersed.Cool to room temperature,and transfer an accurately measured volume of the solution,equivalent to about 0.8mg of chlorpheniramine maleate,to a 100-mLvolumetric flask.Dilute with water to volume,mix,and filter.

System suitability solution— Mix 1part of the Standard preparationprepared above with 1part of the Standard preparation,prepared as directed in the Assay for pseudoephedrine hydrochloride.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm ×15-cm column that contains packing L11.The flow rate is about 2mLper minute.Inject about 20µLof the System suitability solution,and record the peak responses as directed for Procedure:the resolution,R,between pseudoephedrine and chlorpheniramine is not less than 2.0.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor for the chlorpheniramine 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 chlorpheniramine peaks.Calculate the quantity,in mg,of chlorpheniramine maleate (C16H19ClN2·C4H4O4)in the portion of Capsules taken by the formula: in which Cis the concentration,in µg per mL,of USP Chlorpheniramine Maleate RSin the Standard preparation;and rUand rSare the chlorpheniramine peak responses obtained from the Assay preparationand the Standard preparation,respectively.

Mobile phase andChromatographic system— Proceed as directed in the Assay for chlorpheniramine maleate.

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 about 1.0mLof this solution to a 25-mLvolumetric flask,dilute with 0.1%phosphoric acid to volume,and mix.

System suitability solution— Mix 1part of the Standard preparationprepared above with 1part of the Standard preparationprepared as directed in the Assay for chlorpheniramine maleate.

Assay preparation— Transfer not fewer than 10Capsules to a suitable container.Add 100mLof water and 10mLof a phosphoric acid solution (1in 20),and heat gently until the Capsules are fully dispersed.Cool to room temperature,and transfer an accurately measured volume of the solution,equivalent to about 12mg of pseudoephedrine hydrochloride,to a 100-mLvolumetric flask.Dilute with water to volume,mix,and filter.

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 portion of Capsules 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.