Oral Powder Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Pseudoephedrine

» Oral Powder Containing at Least Three of the Following—Acetaminophen and Salts of Chlorpheniramine, Dextromethorphan, and Pseudoephedrine contains not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of acetaminophen (C8H9NO2), chlorpheniramine maleate (C16H19ClN2·C4H4O4), dextromethorphan hydrobromide (C18H25NO·HBr·H2O), and pseudoephedrine hydrochloride (C10H15NO·HCl) or pseudoephedrine sulfate [(C10H15NO)2·H2SO4].

[note—The heading of this monograph does not constitute the official title. It is not intended that the name described herein be recognized as the official title or the common or usual name. The name for each article encompassed by this monograph shall be composed of the names of the active ingredients contained therein, as well as the quantitative amount of each active ingredient, and a statement of the function (or purpose) of the ingredient in the article. ]

Packaging and storage— Preserve in tight containers, and store at controlled room temperature.

USP Reference standards

—

USP Acetaminophen RS

USP Chlorpheniramine Maleate RS

USP Dextromethorphan Hydrobromide RS

USP Pseudoephedrine Hydrochloride RS

USP Pseudoephedrine Sulfate RS

Labeling— The label for each article encompassed by this monograph bears a name composed of the active ingredients. The label states the name and quantity of each active ingredient and indicates its function (or purpose) in the article.

Identification—

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.

Minimum fill

755

: meets the requirements.

Uniformity of dosage units

905

—

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

Assay for pseudoephedrine hydrochloride (where pseudoephedrine hydrochloride is the salt form used, if present in the formulation)—

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:

(CL/D)(rU / rS)

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.

Assay for pseudoephedrine sulfate (where pseudoephedrine sulfate is the salt form used, if present in the formulation)—

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 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:

(CL/D)(rU / rS)

in which the terms are as defined therein, pseudoephedrine sulfate being substituted for pseudoephedrine hydrochloride.

Assay for acetaminophen (if present)—

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

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:

(CL/D)(rU / rS)

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.

Assay for chlorpheniramine maleate (if present)—

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

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:

(CL/D)(rU / rS)

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.

Assay for dextromethorphan hydrobromide (if present)—

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:

(370.33/352.32)(CL/D)(rU / rS)

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.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Clydewyn M. Anthony, Ph.D. Senior Scientific Liaison 1-301-816-8139	(SM22010) Monographs - Small Molecules 2
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org

USP35–NF30 Page 2045

Pharmacopeial Forum: Volume No. 30(1) Page 44