Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine,Dextromethorphan,and Phenylpropanolamine »Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine,Dextromethorphan,and Phenylpropanolamine contain not less than 90.0percent and not more than 110.0percent of the labeled amounts of acetaminophen (C8H9NO2),chlorpheniramine maleate (C16H19ClN2·C4H4O4),dextromethorphan hydrobromide (C18H25NO·HBr·H2O),and phenylpropanolamine hydrochloride (C9H13NO·HCl). NOTE—The heading of this monograph does not constitute the official title.It is not intended that the name described herein be recognized as the official title or the common or usual name.The name for each article encompassed by this monograph shall be composed of the names of the active ingredients contained therein as well as the quantitative amount of each active ingredient,and a statement of the function (or purpose)of the ingredient in the article. Packaging and storage— Preserve in tight containers. USP Reference standards á11ñ USP Acetaminophen RS.USP Chlorpheniramine Maleate RS.USP Dextromethorphan Hydrobromide RS.USP Phenylpropanolamine Hydrochloride RS. Labeling— The label for each article encompassed by this monograph bears a name composed of the active ingredients.The label states the name and quantity of each active ingredient and indicates its function (or purpose)in the article. Identification— A: If phenylpropanolamine hydrochloride is claimed in the labeling to be present,the retention time of the major peak for phenylpropanolamine in the chromatogram of the Phenylpropanolamine assay preparationcorresponds to that in the chromatogram of the Phenylpropanolamine standard preparation,as obtained in the Assay for phenylpropanolamine hydrochloride. 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 Chlorpheniramine assay preparationcorresponds to that in the chromatogram of the Chlorpheniramine 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 Dextromethorphan assay preparationcorresponds to that in the chromatogram of the Dextromethorphan standard preparation,as obtained in the Assay for dextromethorphan hydrobromide. Dissolution,Procedure for a Pooled Sample á711ñ Medium: 0.1Mhydrochloric acid;900mL. Apparatus 2: 50rpm. Time: 45minutes. Test solution— Mix 9.0mLof a filtered portion of the solution under test with 1.0mLof 1%phosphoric acid solution. Procedure— Determine the amounts of phenylpropanolamine hydrochloride,acetaminophen,chlorpheniramine maleate,and dextromethorphan hydrobromide dissolved,employing the procedures set forth in the Assay for phenylpropanolamine hydrochloride,Assay for acetaminophen,Assay for chlorpheniramine maleate,and Assay for dextromethorphan hydrobromide,respectively,making any necessary volumetric adjustments. Tolerances— Not less than 75%(Q)of the labeled amounts of phenylpropanolamine hydrochloride (C9H13NO·HCl),acetaminophen (C8H9NO2),chlorpheniramine maleate (C16H19ClN2·C4H4O4),and dextromethorphan hydrobromide (C18H25NO·HBr ·H2O)is dissolved in 45minutes. Uniformity of dosage units á905ñ: meet the requirements. Assay for phenylpropanolamine hydrochloride— Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40)containing 0.34g of monobasic potassium phosphate,0.05g 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). Phenylpropanolamine standard preparation— Dissolve an accurately weighed quantity of USP Phenylpropanolamine Hydrochloride RSin water to obtain a solution having a known concentration of about 2.5mg per mL.Transfer 1.0mLof this solution to a 50-mLvolumetric flask,add 5mLof methanol,dilute with 0.1%phosphoric acid to volume,and mix. Chlorpheniramine standard preparation— Prepare as directed in the Assay for chlorpheniramine maleate. Dextromethorphan standard preparation— Prepare as directed in the Assay for dextromethorphan hydrobromide. System suitability solution 1 (for Tablets that contain either all the four ingredients or a combination of three containing chlorpheniramine salt)—Mix equal volumes of the Phenylpropanolamine standard preparationand the Chlorpheniramine standard preparation. System suitability solution 2 (for Tablets that contain no chlorpheniramine salt)—Mix equal volumes of the Phenylpropanolamine standard preparationand the Dextromethorphan standard preparation. Phenylpropanolamine assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed quantity of the powder,equivalent to about 2.5mg of phenylpropanolamine hydrochloride,to a 50-mLvolumetric flask.Add 5mLof methanol,and sonicate to disperse the powder.Dilute with 0.1%phosphoric acid to volume,mix,and filter. 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.Chromatograph the Phenylpropanolamine standard preparation,and record the peak responses as directed for Procedure:the tailing factor for the phenylpropanolamine peak is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.Separately inject about 20µLof System suitability solution 1or System suitability solution 2,as appropriate:the resolution,R,between phenylpropanolamine and chlorpheniramine or between phenylpropanolamine and dextromethorphan is not less than 2.0. Procedure— Separately inject equal volumes (about 20µL)of the Phenylpropanolamine standard preparationand the Phenylpropanolamine assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the phenylpropanolamine peaks.Calculate the quantity,in mg,of phenylpropanolamine hydrochloride (C9H13NO·HCl)in the portion of Tablets taken by the formula: 50C(rU/rS), in which Cis the concentration,in mg per mL,of USP Phenylpropanolamine Hydrochloride RSin the Phenylpropanolamine standard preparation;and rUand rSare the peak responses obtained from the Phenylpropanolamine assay preparationand the Phenylpropanolamine standard preparation,respectively. Assay for acetaminophen (if present)— Mobile phase— Prepare a filtered and degassed mixture of water,methanol,and glacial acetic acid (79:20:1).Make adjustments,if necessary (see System Suitabilityunder Chromatography á621ñ). Standard preparation— Transfer about 50mg of USP Acetaminophen RS,accurately weighed,to a 100-mLvolumetric flask.Add 4mLof methanol,and mix until dissolved.Dilute with 0.1%phosphoric acid to volume,and mix. Assay preparation— Weigh and powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 100mg of acetaminophen,to a 50-mLvolumetric flask.Add about 7.5mLof methanol,and sonicate to disperse the powder.Add 0.5mLof phosphoric acid,dilute with water to volume,mix,and filter.Transfer 25.0mLof the filtered solution to a 100-mLvolumetric flask,dilute with water to volume,and mix. Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm ×15-cm column that contains packing L7.The flow rate is about 1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor for the acetaminophen peak is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 5µL)of the Standard preparationand 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 the portion of Tablets taken by the formula: 200C(rU/rS), in which Cis the concentration,in mg per mL,of USP Acetaminophen RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively. Assay for chlorpheniramine maleate (if present)— Mobile phase,Phenylpropanolamine standard preparation,System suitability solution 1,and Chromatographic system— Proceed as directed in the Assay for phenylpropanolamine hydrochloride. Chlorpheniramine 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. Chlorpheniramine assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 0.4mg of chlorpheniramine maleate,to a 50-mLvolumetric flask.Add 5mLof methanol,and sonicate to disperse the powder.Add 0.2mLof phosphoric acid,dilute with water to volume,mix,and filter. Procedure— Separately inject equal volumes (about 20µL)of the Chlorpheniramine standard preparationand the Chlorpheniramine 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 Tablets taken by the formula: 50C(rU/rS), in which Cis the concentration,in mg per mL,of USP Chlorpheniramine Maleate RSin the Chlorpheniramine standard preparation;and rUand rSare the peak responses obtained from the Chlorpheniramine assay preparationand the Chlorpheniramine standard preparation,respectively. Assay for dextromethorphan hydrobromide (if present)— Mobile phase,Phenylpropanolamine standard preparation,and Chromatographic system— Proceed as directed in the Assay for phenylpropanolamine hydrochloride. System suitability solution 1or System suitability solution 2(as appropriate) Proceed as directed in the Assay for phenylpropanolamine hydrochloride. Dextromethorphan standard preparation— Dissolve an accurately weighed quantity of USP Dextromethorphan Hydrobromide RSin water to obtain a solution having a known concentration of about 0.6mg per mL.Quantitatively dilute a portion of this solution with 0.1%phosphoric acid to obtain a solution having a known concentration of about 0.06mg per mL. Dextromethorphan assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 3mg of dextromethorphan hydrobromide,to a 50-mLvolumetric flask.Add 5mLof methanol,and sonicate to disperse the powder.Add 0.2mLof phosphoric acid,dilute with water to volume,mix,and filter. Procedure— Separately inject equal volumes (about 20µL)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 the portion of Tablets taken by the formula: (370.33/352.32)50C(rU/rS), 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;and rUand rSare the dextromethorphan peak responses obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist Expert Committee:(PA2)Pharmaceutical Analysis 2 USP28–NF23Page 25 Pharmacopeial Forum:Volume No.30(1)Page 42 Phone Number:1-301-816-8139