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 Solution Packaged In Single-Unit Containers: meets the requirements.

For Oral Solution Packaged In Multiple-Unit Containers: meets the requirements.

(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, 0.15 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).

Standard preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RS in water to obtain a solution having a known concentration of about 1.5 mg per mL. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, add 8.0 mL of Mobile phase, dilute with water to volume, and mix.

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 Oral Powder that contains 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 Oral Powder that contains no chlorpheniramine salt)— Mix equal volumes of the Standard preparation and the Dextromethorphan standard preparation.

Assay preparation— Transfer an accurately measured volume of the Oral Solution, equivalent to 15 mg of pseudoephedrine hydrochloride, to a 100-mL volumetric flask, add 80.0 mL of Mobile phase, dilute with water to volume, and mix.

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 each mL of the Oral Solution taken by the formula: in which C is the concentration, in mg per mL, of USP Pseudoephedrine Hydrochloride RS in the Standard preparation; V is the volume, in mL, of the Oral Solution taken; and rU and rS are the pseudoephedrine peak responses obtained from the Assay preparation and the Standard preparation, respectively.

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

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 3.0 mg per mL. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, add 4.0 mL of Mobile phase, dilute with water to volume, and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to 30 mg of pseudoephedrine sulfate, to a 100-mL volumetric flask, add 80.0 mL of Mobile phase, dilute with water to volume, and mix.

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 mL of the Oral Solution taken by the formula: in which the terms are as defined therein, pseudoephedrine sulfate being substituted for pseudoephedrine hydrochloride.

Mobile phase— Prepare a suitable degassed and filtered mixture of water, methanol, and glacial acetic acid (79:20:1). Make any necessary adjustments (see System Suitability under Chromatography 621).

Standard preparation— Transfer about 16.5 mg of USP Acetaminophen RS, accurately weighed, to a 100-mL volumetric flask. Add 2.5 mL of methanol, and mix until solution is complete. Dilute with water to volume, and mix to obtain a solution having a known concentration of about 0.165 mg per mL.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 33 mg of acetaminophen, to a 200-mL volumetric flask, add 5 mL of methanol, and mix. 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 each mL of the Oral Solution taken by the formula: in which C is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; V is the volume, in mL, of the Oral Solution taken; 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 1 mg per mL. Transfer 1.0 mL of this solution to a 100-mL volumetric flask, add 80 mL of Mobile phase, dilute with water to volume, and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 1 mg of chlorpheniramine maleate, to a 100-mL volumetric flask. Add 80 mL of Mobile phase, dilute with water to volume, and mix.

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 Oral Solution taken by the formula: in which C is the concentration, in mg per mL, of USP Chlorpheniramine Maleate RS in the Standard preparation; V is the volume, in mL, of the Oral Solution taken; 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.

Standard preparation— Dissolve an accurately weighed quantity of USP Dextromethorphan Hydrobromide RS in water to obtain a solution having a known concentration of about 1.5 mg per mL. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, add 80 mL of Mobile phase, dilute with water to volume, and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 7.5 mg of dextromethorphan hydrobromide, to a 100-mL volumetric flask, add 80 mL of Mobile phase, dilute with water to volume, and mix.

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 mL of the Oral Solution 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; V is the volume, in mL, of the Oral Solution taken; and rU and rS are the dextromethorphan peak responses obtained from the Assay preparation and the Standard preparation, respectively.