Acetaminophen, Dextromethorphan Hydrobromide, Doxylamine Succinate, and Pseudoephedrine Hydrochloride Oral Solution
» Acetaminophen, Dextromethorphan Hydrobromide, Doxylamine Succinate, and Pseudoephedrine Hydrochloride Oral Solution contains not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of Acetaminophen (C8H9NO2), Dextromethorphan Hydrobromide (C18H25NO·HBr·H2O), Doxylamine Succinate (C17H22N2O·C4H6O4), 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 Dextromethorphan Hydrobromide RS Click to View Structure
USP Doxylamine Succinate 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 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.
C: The retention time of the major peak for doxylamine in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay for doxylamine succinate.
D: 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.
Uniformity of dosage units 905
for oral solution packaged in single-unit containers: meets the requirements.
Deliverable volume 698
for oral solution packaged in multiple-unit containers: meets the requirements.
pH 791: between 4.5 and 6.3.
Alcohol content (if present), Method II 611: between 90.0% and 110.0% of the labeled amount of C2H5OH.
Microbial enumeration tests 61 and Tests for specified microorganisms 62 The total bacterial count does not exceed 100 cfu per g, the total combined molds and yeasts count does not exceed 10 cfu per g, and it meets the requirements of the tests for absence of Salmonella species and Escherichia coli.
Assay for acetaminophen—
Mobile phase— Prepare a filtered and degassed mixture of water and methanol (55:45). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Acetaminophen RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.2 mg per mL.
Assay preparation— Dissolve an accurately measured volume of Oral Solution, equivalent to about 200 mg of acetaminophen, in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a concentration of about 0.2 mg of acetaminophen per mL.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency, determined from the analyte peak, is not less than 500 theoretical plates; 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:
(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 per mL, of acetaminophen in the Oral Solution; D is the concentration, in mg per mL, of acetaminophen in the Assay preparation; and rU and rS are the acetaminophen peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for dextromethorphan hydrobromide—
0.05 M Buffer solution— Dissolve 6.8 g of monobasic potassium phosphate in 1 L of water.
Mobile phase— Prepare a filtered and degassed mixture of 0.05 M Buffer solution and acetonitrile (55:45). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve accurately weighed quantities of USP Dextromethorphan Hydrobromide RS, USP Doxylamine Succinate RS, and USP Pseudoephedrine Hydrochloride RS in Mobile phase, and, dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having known concentrations of about 0.1, 0.04, and 0.2 mg per mL, respectively.
Assay preparation— Dissolve an accurately measured volume of Oral Solution, equivalent to about 5 mg of dextromethorphan hydrobromide, in Mobile phase, and quantitatively dilute with Mobile phase to obtain a solution having a concentration of about 0.1 mg per mL.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L9. The flow rate is about 2.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.38 for pseudoephedrine, 0.65 for dextromethorphan, and 1.0 for doxylamine; the tailing factors for the dextromethorphan, doxylamine, and pseudoephedrine peaks are not more than 2.5; the column efficiencies for the dextromethorphan, doxylamine, and pseudoephedrine peaks are not less than 500; and the relative standard deviations of the dextromethorphan, doxylamine, and pseudoephedrine responses for replicate injections are 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 dextromethorphan peak responses. Calculate the quantity, in mg per mL, of dextromethorphan hydrobromide (C18H25NO·HBr·H2O) in the portion of Oral Solution 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 per mL, of dextromethorphan hydrobromide in the Oral Solution; D is the concentration, in mg per mL, of dextromethorphan hydrobromide in the Assay preparation; and rU and rS are the dextromethorphan peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for doxylamine succinate—
0.05 M Buffer solution, Mobile phase, Standard preparation, and Chromatographic system— Proceed as directed in the Assay for dextromethorphan hydrobromide.
Assay preparation— Dissolve an accurately measured volume of Oral Solution, equivalent to about 2 mg of doxylamine succinate, in Mobile phase, and dilute with Mobile phase to obtain a solution having a concentration of about 0.04 mg per mL.
Procedure— Proceed as directed for Procedure in the Assay for dextromethorphan hydrobromide. Calculate the quantity, in mg per mL, of doxylamine succinate (C17H22N2O·C4H6O4) in the portion of Oral Solution taken by the formula:
(CL/D)(rU / rS)
in which C is the concentration, in mg per mL, of USP Doxylamine Succinate RS in the Standard preparation; L is the labeled quantity, in mg per mL, of doxylamine succinate in the Oral Solution; D is the concentration, in mg per mL, of doxylamine succinate in the Assay preparation; and rU and rS are the doxylamine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for pseudoephedrine hydrochloride—
0.05 M Buffer solution, Mobile phase, Standard preparation, and Chromatographic system— Proceed as directed in the Assay for dextromethorphan hydrobromide.
Assay preparation— Dissolve an accurately measured volume of Oral Solution, equivalent to about 10 mg of pseudoephedrine hydrochloride, in Mobile phase, and dilute with Mobile phase to obtain a solution having a concentration of about 0.2 mg per mL.
Procedure— Proceed as directed for Procedure in the Assay for dextromethorphan hydrobromide. Calculate the quantity, in mg per mL, of pseudoephedrine hydrochloride (C10H15NO·HCl) in the portion of Oral Solution 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 amount, in mg per mL, of pseudoephedrine hydrochloride in the Oral Solution; D is the concentration, in mg per mL, of pseudoephedrine hydrochloride in the Assay preparation; and rU and rS are the pseudoephedrine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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