A: If pseudoephedrine hydrochloride or pseudoephedrine sulfate is claimed in the labeling to be present, the chromatogram of the Assay preparation, obtained as directed in the Assay for pseudoephedrine hydrochloride or the Assay for pseudoephedrine sulfate, exhibits a major peak for pseudoephedrine, the retention time of which corresponds to that exhibited by the Standard preparation.

B: If acetaminophen is claimed in the labeling to be present, 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.

C: If chlorpheniramine maleate is claimed in the labeling to be present, 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.

D: If dextromethorphan hydrobromide is claimed in the labeling to be present, 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.

Medium: water; 900 mL.

Apparatus 2: 50 rpm.

Time: 45 minutes.

Test preparation— 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 pseudoephedrine hydrochloride or pseudoephedrine sulfate (as appropriate), acetaminophen, chlorpheniramine maleate, and dextromethorphan hydrobromide dissolved, employing the procedures set forth in the Assay for pseudoephedrine hydrochloride or Assay for pseudoephedrine sulfate, 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 pseudoephedrine hydrochloride (C10H15NO·HCl) or pseudoephedrine sulfate [(C10H15NO)2·H2SO4], acetaminophen (C8H9NO2), chlorpheniramine maleate (C16H19ClN2 · C4H4O4), and dextromethorphan hydrobromide (C18H25NO · HBr · H2O) are dissolved in 45 minutes.

(Official January 1, 2007)

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).

Standard 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.

Chlorpheniramine standard preparation— Prepare as directed for the Standard preparation in the Assay for chlorpheniramine maleate.

Dextromethorphan standard preparation— Prepare as directed for the Standard preparation 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 Standard preparation and the Chlorpheniramine standard preparation.

System suitability solution 2 (for Tablets that contain no chlorpheniramine salt)—Mix equal volumes of the Standard preparation and the Dextromethorphan standard preparation.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed quantity of the powder, equivalent to about 6 mg of pseudoephedrine 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 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%. Separately inject about 10 µL of System suitability solution 1 or System suitability solution 2, as appropriate. The resolution, R, between pseudoephedrine and chlorpheniramine or 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 responses for the pseudoephedrine peaks. Calculate the quantity, in mg, of pseudoephedrine hydrochloride (C10H15NO · HCl) in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Pseudoephedrine Hydrochloride RS in the Standard preparation, and rU and rS are the pseudoephedrine peak responses obtained from the Assay preparation and the Standard preparation, respectively.

Mobile phase, Chlorpheniramine standard preparation, Dextromethorphan standard preparation, System suitability solutions, and Chromatographic system— Proceed as directed in the Assay for pseudoephedrine hydrochloride.

Standard preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Sulfate RS in water to obtain a solution having a known concentration of about 3.0 mg per mL. Transfer 2.0 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.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed quantity of the powder, equivalent to about 12 mg of pseudoephedrine sulfate, 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.

Procedure— Proceed as directed for Procedure in the Assay for pseudoephedrine hydrochloride. Calculate the quantity, in mg, of pseudoephedrine sulfate [(C10H15NO)2 · H2SO4] in the portion of Tablets taken by the formula: in which the terms are as defined therein, pseudoephedrine sulfate being substituted for pseudoephedrine hydrochloride.

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: 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.

Mobile phase and Chromatographic system— Proceed as directed in the Assay for pseudoephedrine hydrochloride.

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.

Assay preparation— Weigh and finely 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 25 mL of methanol, and sonicate to disperse the powder. Add 1 mL of phosphoric acid, dilute with water to volume, mix, and filter.

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: 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.

Mobile phase and Chromatographic system— Proceed as directed in the Assay for pseudoephedrine hydrochloride.

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.

Assay preparation— Weigh and finely 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.

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: 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.