Acetaminophen, Chlorpheniramine Maleate, and Dextromethorphan Hydrobromide Tablets
» Acetaminophen, Chlorpheniramine Maleate, and Detromethorphan Hydrobromide Tablets 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), and dextromethorphan hydrobromide (C18H25NO·HBr·H2O).
Packaging and storage— Preserve in tight containers, and store at controlled room temperature.
Labeling— The label states the name and quantity of each active ingredient and indicates its function (or purpose) in the article. When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
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 Pseudoephedrine Hydrochloride RS Click to View Structure
Identification—
A: The chromatogram of the Assay preparation, obtained as directed in the Assay for acetaminophen, exhibits a major peak for acetaminophen, the retention time of which corresponds to that exhibited by the Standard preparation.
B: The chromatogram of the Assay preparation, obtained as directed in the Assay for chlorpheniramine maleate, exhibits a major peak for chlorpheniramine, the retention time of which corresponds to that exhibited by the Standard preparation.
C: The chromatogram of the Assay preparation, obtained as directed in the Assay for dextromethorphan hydrobromide, exhibits a major peak for dextromethorphan, the retention time of which corresponds to that exhibited by the Standard preparation.
Dissolution, Procedure for a Pooled Sample 711
test 1—
Medium: water; 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 acetaminophen, chlorpheniramine maleate, and dextromethorphan hydrobromide dissolved, employing the procedures set forth in the 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 acetaminophen (C8H9NO2), chlorpheniramine maleate (C16H19ClN2·C4H4O4), and dextromethorphan hydrobromide (C18H25NO·HBr·H2O) are dissolved in 45 minutes.
test 2— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium: 0.1 M hydrochloric acid; 900 mL.
Apparatus, Time, Test solution, Procedure, and Tolerances— Proceed as directed for Test 1.
test 3— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium: pH 5.8 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions); 900 mL.
Apparatus, Time, Test solution, Procedure, and Tolerances— Proceed as directed for Test 1.
Uniformity of dosage units 905: meet the requirements.
Assay for acetaminophen—
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 solution is complete. 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 greater than 2.0, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 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 acetaminophen peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for chlorpheniramine maleate—
Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40) containing 0.34 g of monobasic potassium phosphate, 0.3 g of triethylamine hydrochloride, 0.15 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).
Pseudoephedrine hydrochloride stock preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RS in water to obtain a solution having a known concentration of about 3.0 mg per mL. Transfer 1.0 mL of this solution to a 25-mL volumetric flask, add 2.5 mL of methanol, dilute with 0.1% phosphoric acid to volume, and mix.
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.
System suitability solution— Mix equal volumes of the Pseudoephedrine hydrochloride stock preparation and the Standard preparation.
Assay preparation— Weigh and powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 2 mg of chlorpheniramine maleate, to a 250-mL volumetric flask. Add about 25 mL of methanol, and sonicate to disperse the powder. Add 1 mL of phosphoric acid, dilute with water to volume, mix, and filter.
Chromatographic system— 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 Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the pseudoephedrine peak is not greater than 2.5, and the relative standard deviation for replicate injections is not more than 2.0%. Inject about 10 µL of the System suitability solution; the resolution, R, between pseudoephedrine and chlorpheniramine is not less than 2.0.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the 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:
250C(rU / rS)
in which C is the concentration, in mg per mL, of USP Chlorpheniramine Maleate RS in the Standard preparation; and rU and rS are the peak responses for chlorpheniramine obtained from the Assay preparation and the Standard preparation, respectively.
Assay for dextromethorphan hydrobromide—
Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40) containing 0.34 g of monobasic potassium phosphate, 0.3 g of triethylamine hydrochloride, 0.15 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).
Pseudoephedrine hydrochloride stock preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RS in water to obtain a solution having a known concentration of about 3.0 mg per mL. Transfer 1.0 mL of this solution to a 25-mL volumetric flask, add 2.5 mL of methanol, dilute with 0.1% phosphoric acid to volume, and mix.
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.
System suitability solution— Mix equal volumes of the Pseudoephedrine hydrochloride stock preparation and the Standard preparation.
Assay preparation— Weigh and powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 6 mg of dextromethorphan hydrobromide, to a 100-mL volumetric flask. Add 10 mL of methanol, and sonicate to disperse the powder. Add 0.4 mL of phosphoric acid, dilute with water to volume, mix, and filter.
Chromatographic system— 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 Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the pseudoephedrine peak is not greater than 2.5, and the relative standard deviation for replicate injections is not more than 2.0%. Inject about 10 µL of the System suitability solution; the resolution, R, between pseudoephedrine and dextromethorphan is not less than 2.0.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak 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)(100C)(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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