(Official April 1, 2006)

A: The retention time of the major peak for chlorpheniramine maleate 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.

B: The retention time of the major peak for pseudoephedrine hydrochloride 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.

Test 1— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 1.

Test 2— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 2.

Test 1— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1.

Test 2— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

(Official April 1, 2006)

(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 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 a phosphoric acid solution (1 in 1000) to obtain a solution having a known concentration of about 8 µg per mL.

Assay preparation— Transfer not fewer than 10 Capsules to a suitable container. Add 100 mL of water and 10 mL of a phosphoric acid solution (1 in 20), and heat gently until the Capsules are fully dispersed. Cool to room temperature, and transfer an accurately measured volume of the solution, equivalent to about 0.8 mg of chlorpheniramine maleate, to a 100-mL volumetric flask. Dilute with water to volume, mix, and filter.

System suitability solution— Mix 1 part of the Standard preparation prepared above with 1 part of the Standard preparation, prepared as directed in the Assay for pseudoephedrine hydrochloride.

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. Inject about 20 µL of the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between pseudoephedrine and chlorpheniramine is not less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the chlorpheniramine 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 chlorpheniramine peaks. Calculate the quantity, in mg, of chlorpheniramine maleate (C16H19ClN2·C4H4O4) in the portion of Capsules taken by the formula: in which C is the concentration, in µg per mL, of USP Chlorpheniramine Maleate RS in the Standard preparation; 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 chlorpheniramine maleate.

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 about 1.0 mL of this solution to a 25-mL volumetric flask, dilute with 0.1% phosphoric acid to volume, and mix.

System suitability solution— Mix 1 part of the Standard preparation prepared above with 1 part of the Standard preparation prepared as directed in the Assay for chlorpheniramine maleate.

Assay preparation— Transfer not fewer than 10 Capsules to a suitable container. Add 100 mL of water and 10 mL of a phosphoric acid solution (1 in 20), and heat gently until the Capsules are fully dispersed. Cool to room temperature, and transfer an accurately measured volume of the solution, equivalent to about 12 mg of pseudoephedrine hydrochloride, to a 100-mL volumetric flask. 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 pseudoephedrine peaks. Calculate the quantity, in mg, of pseudoephedrine hydrochloride (C10H15NO·HCl) in the portion of Capsules 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.