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

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 Assay preparation corresponds to that in the chromatogram of the 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 Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay for dextromethorphan hydrobromide.

for oral powder packaged in single-unit containers: meets the requirements.

(Official January 1, 2007)

Mobile phase and Chromatographic system— Proceed as directed in the Assay for pseudoephedrine hydrochloride under Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Pseudoephedrine.

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.

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 2.0 mL of this solution to a 25-mL volumetric flask, dilute with 0.1% phosphoric acid to volume, and mix.

System suitability solution 1 (for Oral Powder that contains either all 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 Oral Powder that contains no chlorpheniramine salt)— Mix equal volumes of the Standard preparation and the Dextromethorphan standard preparation.

Assay preparation— Transfer the contents of 10 unit-dose containers of the Oral Powder to a 2000-mL volumetric flask. Add 1000 mL of water and 2.0 mL of phosphoric acid. Gently heat to about 60 until the powder is fully dispersed. Cool the flask to room temperature, add 40 mL of methanol, 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 0.24 mg of pseudoephedrine 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 pseudoephedrine peaks. Calculate the quantity, in mg, of pseudoephedrine hydrochloride (C10H15NO·HCl), in each unit-dose container of Oral Powder taken by the formula: in which C is the concentration, in mg per mL, of USP Pseudoephedrine Hydrochloride RS in the Standard preparation; L is the labeled quantity, in mg, of pseudoephedrine hydrochloride in each unit-dose container; D is the concentration, in mg per mL, of pseudoephedrine hydrochloride in each mL of the Assay preparation, based on the number of unit-dose containers taken, the labeled quantity, in mg, of pseudoephedrine hydrochloride in each unit-dose container, and the extent of dilution; and rU and rS are the pseudoephedrine 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 under Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Pseudoephedrine.

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.

Standard preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Sulfate RS in water to obtain a solution having a known concentration of about 6.0 mg per mL. Transfer 2.0 mL of this solution to a 25-mL volumetric flask, dilute with 0.1% phosphoric acid to volume, and mix.

System suitability solution 1 (for Oral Powder that contains either all 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 Oral Powder that contains no chlorpheniramine salt)—Mix equal volumes of the Standard preparation and the Dextromethorphan standard preparation.

Assay preparation— Proceed as directed for the Assay preparation in the Assay for pseudoephedrine hydrochloride to obtain a solution having a concentration of about 0.48 mg of pseudoephedrine sulfate per mL.

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

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

Assay preparation— Transfer the contents of 10 unit-dose containers of the Oral Powder to a 2000-mL volumetric flask. Add 1000 mL of water and 2 mL of phosphoric acid. Gently heat to about 60 until the powder is fully dispersed. Cool the flask to room temperature, add 40 mL of methanol, 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 0.50 mg of acetaminophen 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 acetaminophen peaks. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in each unit-dose container of Oral Powder 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 unit-dose container; D is the concentration, in mg per mL, of acetaminophen in the Assay preparation, based on the number of unit-dose containers taken, the labeled quantity, in mg, of acetaminophen in each unit-dose container, 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 pseudoephedrine hydrochloride under Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Pseudoephedrine.

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 the contents of 10 unit-dose containers of Oral Powder to a 2000-mL volumetric flask. Add 1000 mL of water and 2 mL of phosphoric acid. Gently heat to about 60 until the powder is fully dispersed. Cool the flask to room temperature, add 40 mL of methanol, 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 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 unit-dose container of Oral Powder 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 unit-dose container; D is the concentration, in mg per mL, of chlorpheniramine maleate in each mL of the Assay preparation, based on the number of unit-dose containers taken, the labeled quantity, in mg, of chlorpheniramine maleate in each unit-dose container, 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 pseudoephedrine hydrochloride under Tablets Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Pseudoephedrine.

Standard preparation— Dissolve an accurately weighed quantity of USP Dextromethorphan Hydrobromide RS in water to obtain a solution having a known concentration of about 0.8 mg per mL. Quantitatively dilute a portion of this solution with 0.1% phosphoric acid to obtain a solution having a known concentration of 0.08 mg per mL.

Assay preparation— Transfer the contents of 10 unit-dose containers of Oral Powder to a 2000-mL volumetric flask. Add 1000 mL of water and 2 mL of phosphoric acid. Gently heat to about 60 until the powder is fully dispersed. Cool the flask to room temperature, add 40 mL of methanol, dilute with water to volume, and mix. If necessary, quantitatively dilute a portion of this solution with 0.1% phosphoric acid to obtain a solution having a concentration of 0.08 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 unit-dose container of Oral Powder 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 unit-dose container; D is the concentration, in mg per mL, of dextromethorphan hydrobromide in each mL of the Assay preparation, based on the number of unit-dose containers taken, the labeled quantity, in mg, of dextromethorphan hydrobromide in each unit-dose container, and the extent of dilution; and rU and rS are the dextromethorphan peak responses obtained from the Assay preparation and the Standard preparation, respectively.