Acetaminophen, Diphenhydramine Hydrochloride, and Pseudoephedrine Hydrochloride Tablets
» Acetaminophen, Diphenhydramine Hydrochloride, and Pseudoephedrine Hydrochloride Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of acetaminophen (C8H9NO2), diphenhydramine hydrochloride (C17H21NO·HCl), and pseudoephedrine hydrochloride (C10H15NO·HCl).
Packaging and storage— Preserve in tight containers, and store at controlled room temperature.
USP Reference standards 11
USP Acetaminophen RS Click to View Structure
USP Diphenhydramine Hydrochloride RS Click to View Structure
USP Pseudoephedrine Hydrochloride RS Click to View Structure
Identification—
A: 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.
B: The retention time of the major peak for diphenhydramine in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay for diphenhydramine hydrochloride.
C: 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.
Dissolution, Procedure for a Pooled Sample 711
Medium: pH 5.8 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions); 900 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Determine the amounts of acetaminophen (C8H9NO2), diphenhydramine hydrochloride (C17H21NO·HCl), and pseudoephedrine hydrochloride (C10H15NO·HCl) dissolved by employing the following method.
Buffer solution, Diluting solvent, Mobile phase, and Chromatographic system— Proceed as directed in the Assay for acetaminophen.
Standard solution— Prepare as directed for the Standard preparation in the Assay for acetaminophen.
Test solution 1— Combine equal volumes of the filtered solutions under test, and use the pooled sample.
Test solution 2— Transfer 5.0 mL of Test solution 1 to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Procedure— Using Test solution 1 and the Standard solution, and making any necessary volumetric adjustments, proceed as directed in the Assay for diphenhydramine hydrochloride and the Assay for pseudoephedrine hydrochloride, and determine the amounts of diphenhydramine hydrochloride (C17H21NO·HCl) and pseudoephedrine hydrochloride (C10H15NO·HCl) dissolved. Using Test solution 2 and the Standard solution, and making any necessary volumetric adjustments, proceed as directed in the Assay for acetaminophen, and determine the amount of acetaminophen (C8H9NO2) dissolved.
Tolerances— Not less than 75% (Q) of the labeled amounts of C8H9NO2, C17H21NO·HCl, and C10H15NO·HCl is dissolved in 45 minutes.
for tablets labeled as chewable—
Medium: pH 5.8 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions); 900 mL.
Apparatus 2: 75 rpm.
Time: 45 minutes.
Tolerances— Not less than 75% (Q) of the labeled amounts of C8H9NO2, C17H21NO·HCl, and C10H15NO·HCl is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Assay for acetaminophen—
Buffer solution— Transfer 6.8 g of monobasic potassium phosphate to a 1000-mL volumetric flask, and add water to dissolve. Add 2.0 mL of triethylamine, dilute with water to volume, and mix. Adjust with phosphoric acid to a pH of 4.0.
Diluting solvent— Prepare a mixture of Buffer solution and acetonitrile (89:11).
Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (94:6). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve accurately weighed quantities of USP Acetaminophen RS, USP Diphenhydramine Hydrochloride RS, and USP Pseudoephedrine Hydrochloride RS in Diluting solvent, and dilute quantitatively, and stepwise if necessary, with Diluting solvent to obtain a solution having known concentrations of about 0.025 mg per mL, 0.0125 mg per mL, and 0.03 mg per mL, respectively.
Assay preparation— Weigh and finely powder not fewer than 20 Tablets, and transfer an accurately weighed portion of the powder, equivalent to about 500 mg of acetaminophen, to a 100-mL volumetric flask. Add about 75 mL of Diluting solvent, shake, and sonicate for 15 minutes. Cool to room temperature, dilute with Diluting solvent to volume, and mix. Dilute an accurately measured volume of the solution quantitatively, and stepwise if necessary, with Diluting solvent to obtain a solution having a concentration of about 25 µg of acetaminophen per mL.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains packing L10. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiencies, determined from the acetaminophen, diphenhydramine, and pseudoephedrine peaks, are not less than 3000 theoretical plates; the tailing factors for the acetaminophen, diphenhydramine, and pseudoephedrine peaks are not more than 2.0; and the relative standard deviations determined from the acetaminophen, diphenhydramine hydrochloride, and pseudoephedrine hydrochloride responses for replicate injections are not more 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 acetaminophen peak responses. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in the portion of Tablets taken by the formula:
20C(rU / rS)
in which C is the concentration, in µg per mL, of USP Acetaminophen RS in the Standard preparation; and rU and rS are the acetaminophen peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for diphenhydramine hydrochloride—
Buffer solution, Diluting solvent, Mobile phase, Standard preparation, and Chromatographic system— Proceed as directed in the Assay for acetaminophen.
Assay preparation— Weigh and finely powder not fewer than 20 Tablets, and transfer an accurately weighed portion of the powder, equivalent to about 12.5 mg of diphenhydramine hydrochloride, to a 100-mL volumetric flask. Add about 75 mL of Diluting solvent, shake, and sonicate for 15 minutes. Cool to room temperature, dilute with Diluting solvent to volume, and mix. Dilute an accurately measured volume of this solution quantitatively, and stepwise if necessary, with Diluting solvent to obtain a solution having a concentration of about 12.5 µg of diphenhydramine per mL.
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 diphenhydramine peak responses. Calculate the quantity, in mg, of diphenhydramine hydrochloride (C17H21NO·HCl) in the portion of Tablets taken by the formula:
C(rU / rS)
in which C is the concentration, in mg per mL, of USP Diphenhydramine Hydrochloride RS in the Standard preparation; and rU and rS are the diphenhydramine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for pseudoephedrine hydrochloride—
Buffer solution, Diluting solvent, Mobile phase, Standard preparation, and Chromatographic system— Proceed as directed in the Assay for acetaminophen.
Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 30 mg of pseudoephedrine hydrochloride, to a 100-mL volumetric flask, add about 75 mL of Diluting solvent, shake, and sonicate for 15 minutes. Cool to room temperature, dilute with Diluting solvent to volume, and mix. Dilute an accurately measured volume of this solution quantitatively, and stepwise if necessary, with Diluting solvent to obtain a solution having a concentration of about 30 µg of pseudoephedrine hydrochloride per mL.
Procedure— Separately inject equal volumes (about 20 µL) of the Assay preparation and the Standard preparation into the chromatograph, record the chromatograms, and measure the pseudoephedrine peak responses. Calculate the quantity, in mg per mL, of pseudoephedrine hydrochloride (C10H15NO·HCl) in the portion of Tablets taken by the formula:
C(rU / rS)
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.
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
711 Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison
1-301-816-8106
(GCDF2010) General Chapters - Dosage Forms
USP35–NF30 Page 2058
Pharmacopeial Forum: Volume No. 30(1) Page 47