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 90.0 percent and not more than 110.0 percent 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 11
USP Acetaminophen RS Click to View Structure
USP Chlorpheniramine Maleate RS Click to View Structure
USP Dextromethorphan Hydrobromide RS Click to View Structure
USP Phenylpropanolamine Hydrochloride RS Click to View Structure
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 preparation corresponds 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 preparation corresponds 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 preparation corresponds 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 preparation corresponds to that in the chromatogram of the Dextromethorphan standard preparation, as obtained in the Assay for dextromethorphan hydrobromide.
Dissolution, Procedure for a Pooled Sample 711
Medium: 0.1 M hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Test solution— Mix 9.0 mL of a filtered portion of the solution under test with 1.0 mL of 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 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Assay for phenylpropanolamine hydrochloride—
Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40) containing 0.34 g of monobasic potassium phosphate, 0.05 g of triethylamine hydrochloride, 0.25 g of sodium lauryl sulfate, and 0.1 mL of phosphoric acid in each 100 mL of solution. Make adjustments if necessary (see System Suitability under Chromatography 621).
Phenylpropanolamine standard preparation— Dissolve an accurately weighed quantity of USP Phenylpropanolamine Hydrochloride RS in water to obtain a solution having a known concentration of about 2.5 mg per mL. Transfer 1.0 mL of this solution to a 50-mL volumetric flask, add 5 mL of 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 preparation and the Chlorpheniramine standard preparation.
System suitability solution 2 (for Tablets that contain no chlorpheniramine salt)—Mix equal volumes of the Phenylpropanolamine standard preparation and the Dextromethorphan standard preparation.
Phenylpropanolamine assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed quantity of the powder, equivalent to about 2.5 mg of phenylpropanolamine hydrochloride, to a 50-mL volumetric flask. Add 5 mL of methanol, and sonicate to disperse the powder. Dilute with 0.1% phosphoric acid to volume, mix, and filter.
Chromatographic system (see Chromatography 621)— 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 2 mL per 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 20 µL of System suitability solution 1 or 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 20 µL) of the Phenylpropanolamine standard preparation and the Phenylpropanolamine assay preparation into 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 C is the concentration, in mg per mL, of USP Phenylpropanolamine Hydrochloride RS in the Phenylpropanolamine standard preparation; and rU and rS are the peak responses obtained from the Phenylpropanolamine assay preparation and 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 Suitability under Chromatography 621).
Standard preparation— Transfer about 50 mg of USP Acetaminophen RS, accurately weighed, to a 100-mL volumetric flask. Add 4 mL of methanol, and mix until dissolved. Dilute with 0.1% phosphoric acid to volume, and mix.
Assay preparation— Weigh and powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of acetaminophen, to a 50-mL volumetric flask. Add about 7.5 mL of methanol, and sonicate to disperse the powder. Add 0.5 mL of phosphoric acid, dilute with water to volume, mix, and filter. Transfer 25.0 mL of the filtered solution to a 100-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621)— 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 1 mL per 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 5 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and 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 RS in water to obtain a solution having a known concentration of about 0.8 mg per mL. Quantitatively dilute a portion of this solution with 0.1% phosphoric acid to obtain a solution having a known concentration of about 8 µg per mL.
Chlorpheniramine assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 0.4 mg of chlorpheniramine maleate, to a 50-mL volumetric flask. Add 5 mL of methanol, and sonicate to disperse the powder. Add 0.2 mL of phosphoric acid, dilute with water to volume, mix, and filter.
Procedure— Separately inject equal volumes (about 20 µL) of the Chlorpheniramine standard preparation and the Chlorpheniramine assay preparation into 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 C is the concentration, in mg per mL, of USP Chlorpheniramine Maleate RS in the Chlorpheniramine standard preparation; and rU and rS are the peak responses obtained from the Chlorpheniramine assay preparation and 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 1 or 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 RS in water to obtain a solution having a known concentration of about 0.6 mg per mL. Quantitatively dilute a portion of this solution with 0.1% phosphoric acid to obtain a solution having a known concentration of about 0.06 mg per mL.
Dextromethorphan assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 3 mg of dextromethorphan hydrobromide, to a 50-mL volumetric flask. Add 5 mL of methanol, and sonicate to disperse the powder. Add 0.2 mL of phosphoric acid, dilute with water to volume, mix, and filter.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into 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 370.33 and 352.32 are the molecular weights of dextromethorphan hydrobromide monohydrate and anhydrous dextromethorphan hydrobromide, respectively; C is the concentration, in mg per mL, of USP Dextromethorphan Hydrobromide RS in the Standard preparation; and rU and rS are the dextromethorphan peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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