Guaifenesin and Pseudoephedrine Hydrochloride Capsules
» Guaifenesin and Pseudoephedrine Hydrochloride Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of guaifenesin (C10H14O4) and pseudoephedrine hydrochloride (C10H15NO·HCl).
Packaging and storage—
Preserve in tight, light-resistant containers.
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Identification—
A:
The retention time of the guaifenesin peak relative to that of the benzoic acid peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation as obtained in the Assay for guaifenesin.
B:
The retention time of the pseudoephedrine peak in the chromatogram of the Assay preparation relative to that of the dextromethorphan peak corresponds to that in the chromatogram of the Standard preparation as obtained in the Assay for pseudoephedrine hydrochloride.
Uniformity of dosage units 
905
—
905—
Procedure for content uniformity of pseudoephedrine hydrochloride—
Proceed as directed in the Assay for pseudoephedrine hydrochloride, preparing the Assay preparation as follows. Transfer 1 Capsule to a 100-mL volumetric flask, add about 50 mL of water, heat on a steam bath for about 5 minutes, and allow to cool. Add 5.0 mL of Internal standard solution, dilute with water to volume, and mix.
Assay for guaifenesin—
Mobile phase—
Prepare a mixture of water, methanol, and glacial acetic acid (60:40:1.5). Make any necessary adjustments (see System Suitability under Chromatography 621).
621).
Internal standard solution—
Prepare a solution of benzoic acid in methanol containing about 2 mg per mL.
Standard stock solution—
Prepare a solution in water having known concentrations of about 20 mg of USP Guaifenesin RS and 20J mg of USP Pseudoephedrine Hydrochloride RS per mL, J being the ratio of the labeled amount, in mg, of pseudoephedrine hydrochloride to the labeled amount, in mg, of guaifenesin per Capsule.
Standard preparation—
Transfer 10.0 mL of the Standard stock solution to a 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 5.0 mL of this solution and 5.0 mL of Internal standard solution to a second 100-mL volumetric flask, add about 40 mL of methanol, dilute with water to volume, and mix. Each mL of this solution contains about 0.1 mg of USP Guaifenesin RS, 0.1J mg of USP Pseudoephedrine Hydrochloride RS, and 0.1 mg of benzoic acid.
Assay preparation—
Transfer an accurately counted number of Capsules, equivalent to about 2000 mg of guaifenesin, to a 100-mL volumetric flask, add about 50 mL of water, and heat on a steam bath for about 15 minutes. Allow to cool, dilute with water to volume, and mix. Transfer 10.0 mL of this stock solution to a second 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 5.0 mL of this solution and 5.0 mL of Internal standard solution to a third 100-mL volumetric flask, add about 40 mL of methanol, dilute with water to volume, and mix.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 276-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the relative retention times are about 0.65 for guaifenesin and 1.0 for benzoic acid; the resolution, R, between the guaifenesin peak and the benzoic acid peak is not less than 3.0; the tailing factors for the guaifenesin peak and the benzoic acid peak are not more than 2.5; and the relative standard deviation for replicate injections is not more than 2.5%.
621)—The liquid chromatograph is equipped with a 276-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the relative retention times are about 0.65 for guaifenesin and 1.0 for benzoic acid; the resolution, R, between the guaifenesin peak and the benzoic acid peak is not less than 3.0; the tailing factors for the guaifenesin peak and the benzoic acid peak are not more than 2.5; and the relative standard deviation for replicate injections is not more than 2.5%.
Procedure—
[note—Use peak areas where peak responses are indicated. ] 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 major peaks. Calculate the quantity, in mg, of guaifenesin (C10H14O4) in each Capsule taken by the formula:
20,000(C / N)(RU / RS)
in which C is the concentration, in mg per mL, of USP Guaifenesin RS in the Standard preparation; N is the number of Capsules taken; and RU and RS are the ratios of the guaifenesin peak response to the benzoic acid peak response obtained from the Assay preparation and the Standard preparation, respectively.
Assay for pseudoephedrine hydrochloride—
Mobile phase—
To 3.5 g of docusate sodium add 500 mL of methanol, 350 mL of water, 145 mL of tetrahydrofuran, and 5 mL of glacial acetic acid, mix, and pass through a filter having a porosity of 0.5 µm or less. Make any necessary adjustments (see System Suitability under Chromatography 621).
621).
Internal standard solution—
Prepare a solution of dextromethorphan hydrobromide in methanol containing about 1.2 mg per mL.
Standard stock solution—
Prepare as directed in the Assay for guaifenesin.
Standard preparation—
Transfer 10.0 mL of Standard stock solution and 5.0 mL of Internal standard solution to a 100-mL volumetric flask, dilute with water to volume, and mix. Each mL of this solution contains about 2 mg of USP Guaifenesin RS, 2J mg of USP Pseudoephedrine Hydrochloride RS, and 0.06 mg of dextromethorphan hydrobromide.
Assay preparation—
Transfer 10.0 mL of the stock solution used to prepare the Assay preparation in the Assay for guaifenesin and 5.0 mL of Internal standard solution to a 100-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 263-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the relative retention times are about 0.55 for pseudoephedrine and 1.0 for dextromethorphan; the resolution, R, between the pseudoephedrine peak and the dextromethorphan peak is not less than 1.5; the tailing factors for the pseudoephedrine peak and the dextromethorphan peak are not more than 1.5 and 2.5, respectively; and the relative standard deviation for replicate injections determined for the pseudoephedrine peak is not more than 2.0%.
621)—The liquid chromatograph is equipped with a 263-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the relative retention times are about 0.55 for pseudoephedrine and 1.0 for dextromethorphan; the resolution, R, between the pseudoephedrine peak and the dextromethorphan peak is not less than 1.5; the tailing factors for the pseudoephedrine peak and the dextromethorphan peak are not more than 1.5 and 2.5, respectively; and the relative standard deviation for replicate injections determined for the pseudoephedrine peak is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the area responses for the major peaks. Calculate the quantity, in mg, of pseudoephedrine hydrochloride (C10H15NO·HCl) in each Capsule taken by the formula:
1000(C / N)(RU / RS)
in which C is the concentration, in mg per mL, of USP Pseudoephedrine Hydrochloride RS in the Standard preparation; N is the number of Capsules taken; and RU and RS are the ratios of the pseudoephedrine peak area response to the dextromethorphan peak area response 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 3384