A: If phenylpropanolamine hydrochloride is claimed in the labeling to be present, the chromatogram of the Assay preparation, obtained as directed in the Assay for phenylpropanolamine hydrochloride, exhibits a major peak for phenylpropanolamine, 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 1: 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) are dissolved in 45 minutes.

(Official January 1, 2007)

Mobile phase, Standard preparation, and Chromatographic system— Proceed as directed in the Assay for phenylpropanolamine hydrochloride under Oral Solution Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Phenylpropanolamine.

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

Dextromethorphan standard preparation— Prepare as directed for Standard preparation in the Assay for dextromethorphan hydrobromide.

System suitability solution 1 (for Capsules that contain either all four ingredients or a combination of three including chlorpheniramine salt)—Mix equal volumes of the Standard preparation and the Chlorpheniramine standard preparation.

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

Assay preparation— Transfer not less than 10 Capsules, accurately counted, to a 500-mL volumetric flask. Add about 100 mL of water and 10 mL of 5% phosphoric acid, and gently heat until the Capsules are fully dispersed. Cool the solution to room temperature, dilute with water to volume, mix, and filter. Quantitatively dilute a portion of this solution, if necessary, with water to obtain a solution having a concentration of about 0.05 mg of phenylpropanolamine hydrochloride per mL.

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 phenylpropanolamine peaks. Calculate the quantity, in mg, of phenylpropanolamine hydrochloride (C9H13NO · HCl) in the Capsules taken by the formula: in which C is the concentration, in mg per mL, of USP Phenylpropanolamine Hydrochloride RS in the Standard preparation; L is the labeled quantity, in mg, of phenylpropanolamine hydrochloride in each Capsule; D is the concentration, in mg per mL, of phenylpropanolamine hydrochloride in the Assay preparation, based on the number of Capsules taken, the labeled quantity, in mg, of phenylpropanolamine hydrochloride in each Capsule, and the extent of dilution; and rU and rS are the phenylpropanolamine peak responses obtained from the Assay preparation and the Standard preparation, respectively.

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 25 mg of USP Acetaminophen RS, accurately weighed, to a 100-mL volumetric flask. Add 4 mL of methanol, and mix until solution is complete. Add 0.2 mL of phosphoric acid, dilute with water to volume, and mix to obtain a solution having a known concentration of about 0.25 mg per mL.

Assay preparation— Transfer not fewer than 10 Capsules, accurately counted, to a 500-mL volumetric flask. Add about 100 mL of water and 10 mL of 5% phosphoric acid, and gently heat until the Capsules are fully dispersed. Cool the solution to room temperature, dilute with water to volume, and mix. Quantitatively dilute a portion of this solution, if necessary, with 0.1% phosphoric acid to obtain a solution having a concentration of about 0.25 mg of acetaminophen per mL.

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 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 each Capsule taken by the formula: in which C is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; L is the labeled quantity, in mg, of acetaminophen in each Capsule; D is the concentration, in mg per mL, of acetaminophen in each mL of the Assay preparation, based on the number of Capsules taken, the labeled quantity, in mg, of acetaminophen in each Capsule, and the extent of dilution; 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 phenylpropanolamine hydrochloride under Oral Solution Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Phenylpropanolamine.

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— Transfer not fewer than 10 Capsules, accurately counted, to a 500-mL volumetric flask. Add about 100 mL of water and 10 mL of 5% phosphoric acid, and gently heat until the Capsules are fully dispersed. Cool the solution to room temperature, dilute with water to volume, mix, and filter. Quantitatively dilute a portion of this solution, if necessary, with 0.1% phosphoric acid to obtain a solution having a concentration of about 8 µg of chlorpheniramine maleate per mL.

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 each Capsule taken by the formula: in which C is the concentration, in mg per mL, of USP Chlorpheniramine Maleate RS in the Standard preparation; L is the labeled quantity, in mg, of chlorpheniramine maleate in each Capsule; D is the concentration, in mg per mL, of chlorpheniramine maleate in each mL of the Assay preparation, based on the number of Capsules taken, the labeled quantity, in mg, of chlorpheniramine maleate in each Capsule, and the extent of dilution; and rU and rS are the chlorpheniramine peak responses obtained from the Assay preparation and the Standard preparation, respectively.

Mobile phase and Chromatographic system— Proceed as directed in the Assay for phenylpropanolamine hydrochloride under Oral Solution Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Phenylpropanolamine.

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— Transfer not fewer than 10 Capsules, accurately counted, to a 500-mL volumetric flask. Add about 100 mL of water and 10 mL of 5% phosphoric acid, and gently heat until the Capsules are fully dispersed. Cool the solution to room temperature, dilute with water to volume, mix, and filter. Quantitatively dilute a portion of this solution, if necessary, with 0.1% phosphoric acid to obtain a solution having a concentration of about 0.06 mg of dextromethorphan hydrobromide per mL.

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 dextromethorphan peaks. Calculate the quantity, in mg, of dextromethorphan hydrobromide (C18H25NO · HBr · H2O) in each Capsule 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; L is the labeled quantity, in mg, of dextromethorphan hydrobromide in each Capsule; D is the concentration, in mg per mL, of dextromethorphan hydrobromide in each mL of the Assay preparation, based on the number of Capsules taken, the labeled quantity, in mg, of dextromethorphan hydrobromide in each Capsule, and the extent of dilution; and rU and rS are the dextromethorphan peak responses obtained from the Assay preparation and the Standard preparation, respectively.