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.

(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 Phenylpropanolamine Hydrochloride RS in water to obtain a solution having a known concentration of about 0.5 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 Solution 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 Solution 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 2.5 mg of phenylpropanolamine hydrochloride, to a 50-mL volumetric flask, add about 40 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 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the phenylpropanolamine peak is not greater than 2.0; 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 phenylpropanolamine and chlorpheniramine or between phenylpropanolamine and dextromethorphan is not less than 2.0.

Procedure— Separately inject equal volumes (about 20 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 per mL, of phenylpropanolamine hydrochloride (C9H13NO · HCl), in the volume of Oral Solution taken by the formula: in which C is the concentration, in mg per mL, of USP Phenylpropanolamine Hydrochloride RS in the Standard preparation; V is the volume, in mL, of the Oral Solution taken; and rU and rS are the phenylpropanolamine peak responses obtained from the Assay preparation and the Standard preparation, respectively.

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 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 per mL, of acetaminophen (C8H9NO2) in the volume of 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 phenylpropanolamine 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 0.08 mg per mL. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, add 8 mL of Mobile phase, dilute with water to volume, and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 0.4 mg of chlorpheniramine maleate, to a 50-mL volumetric flask. Add 40 mL of Mobile phase, dilute with water to volume, and mix.

Procedure— Separately inject equal volumes (about 20 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 per mL, of chlorpheniramine maleate (C16H19ClN2 · C4H4O4) in the volume of 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 phenylpropanolamine 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 0.4 mg per mL. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, add 8 mL of Mobile phase, dilute with water to volume, and mix.

Assay preparation— Transfer an accurately measured volume of Oral Solution, equivalent to about 2 mg of dextromethorphan hydrobromide, to a 50-mL volumetric flask, add 40 mL of Mobile phase, dilute with water to volume, and mix.

Procedure— Separately inject equal volumes (about 20 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 per mL, of dextromethorphan hydrobromide (C18H25NO · HBr · H2O) in the volume of 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 Oral Solution taken; and rU and rS are the dextromethorphan peak responses obtained from the Assay preparation and the Standard preparation, respectively.