Identification
A:
If phenylpropanolamine hydrochloride is claimed in the labeling to be present, the retention time of the major peak for phenylpropanolamine in the chromatogram of the
Phenylpropanolamine assay preparation corresponds to that in the chromatogram of the
Phenylpropanolamine standard preparation, as obtained in the
Assay for phenylpropanolamine hydrochloride.
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
Chlorpheniramine assay preparation corresponds to that in the chromatogram of the
Chlorpheniramine 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
Dextromethorphan assay preparation corresponds to that in the chromatogram of the
Dextromethorphan standard preparation, as obtained in the
Assay for dextromethorphan hydrobromide.
Dissolution, Procedure for a Pooled Sample
711
Medium:
0.1 M hydrochloric acid; 900 mL.
Apparatus 2:
50 rpm.
Time:
45 minutes.
Test solution
Mix 9.0 mL of a filtered portion of the solution under test with 1.0 mL of 1% phosphoric acid solution.
Tolerances
Not less than 75% (Q) of the labeled amounts of phenylpropanolamine hydrochloride (C9H13NO · HCl), acetaminophen (C8H9NO2), chlorpheniramine maleate (C16H19ClN2 · C4H4O4), and dextromethorphan hydrobromide (C18H25NO · HBr · H2O) is dissolved in 45 minutes.
Assay for phenylpropanolamine hydrochloride
Mobile phase
Prepare a filtered and degassed mixture of methanol and water (60:40) containing 0.34 g of monobasic potassium phosphate, 0.05 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![](images/chars/rang.gif)
).
Phenylpropanolamine standard preparation
Dissolve an accurately weighed quantity of
USP Phenylpropanolamine Hydrochloride RS in water to obtain a solution having a known concentration of about 2.5 mg per mL. Transfer 1.0 mL of this solution to a 50-mL volumetric flask, add 5 mL of methanol, dilute with 0.1% phosphoric acid to volume, and mix.
System suitability solution 1
(for Tablets that contain either all the four ingredients or a combination of three containing chlorpheniramine salt)Mix equal volumes of the Phenylpropanolamine standard preparation and the Chlorpheniramine standard preparation.
System suitability solution 2
(for Tablets that contain no chlorpheniramine salt)Mix equal volumes of the Phenylpropanolamine standard preparation and the Dextromethorphan standard preparation.
Phenylpropanolamine assay preparation
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed quantity of the powder, equivalent to about 2.5 mg of phenylpropanolamine hydrochloride, to a 50-mL volumetric flask. Add 5 mL of methanol, and sonicate to disperse the powder. Dilute with 0.1% phosphoric acid to volume, mix, and filter.
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. Chromatograph the
Phenylpropanolamine standard preparation, and record the peak responses as directed for
Procedure: the tailing factor for the phenylpropanolamine peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%. Separately inject about 20 µL of
System suitability solution 1 or
System suitability solution 2, as appropriate: the resolution,
R, between phenylpropanolamine and chlorpheniramine or between phenylpropanolamine and dextromethorphan is not less than 2.0.
Procedure
Separately inject equal volumes (about 20 µL) of the
Phenylpropanolamine standard preparation and the
Phenylpropanolamine assay preparation into the chromatograph, record the chromatograms, and measure the responses for the phenylpropanolamine peaks. Calculate the quantity, in mg, of phenylpropanolamine hydrochloride (C
9H
13NO · HCl) in the portion of Tablets taken by the formula:
50C(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Phenylpropanolamine Hydrochloride RS in the
Phenylpropanolamine standard preparation; and
rU and
rS are the peak responses obtained from the
Phenylpropanolamine assay preparation and the
Phenylpropanolamine standard preparation, respectively.
Assay for acetaminophen (if present)
Mobile phase
Prepare a filtered and degassed mixture of water, methanol, and glacial acetic acid (79:20:1). Make adjustments, if necessary (see
System Suitability under
Chromatography
621![](images/chars/rang.gif)
).
Standard preparation
Transfer about 50 mg of
USP Acetaminophen RS, accurately weighed, to a 100-mL volumetric flask. Add 4 mL of methanol, and mix until dissolved. Dilute with 0.1% phosphoric acid to volume, and mix.
Assay preparation
Weigh and powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of acetaminophen, to a 50-mL volumetric flask. Add about 7.5 mL of methanol, and sonicate to disperse the powder. Add 0.5 mL of phosphoric acid, dilute with water to volume, mix, and filter. Transfer 25.0 mL of the filtered 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 280-nm detector and a 4.6-mm × 15-cm column that contains packing L7. The flow rate is about 1 mL per minute. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the tailing factor for the acetaminophen peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 5 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 (C
8H
9NO
2) in the portion of Tablets taken by the formula:
200C(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Acetaminophen RS in the
Standard preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
Assay for chlorpheniramine maleate (if present)
Chlorpheniramine 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.
Chlorpheniramine assay preparation
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 0.4 mg of chlorpheniramine maleate, to a 50-mL volumetric flask. Add 5 mL of methanol, and sonicate to disperse the powder. Add 0.2 mL of phosphoric acid, dilute with water to volume, mix, and filter.
Procedure
Separately inject equal volumes (about 20 µL) of the
Chlorpheniramine standard preparation and the
Chlorpheniramine assay preparation into the chromatograph, record the chromatograms, and measure the responses for the chlorpheniramine peaks. Calculate the quantity, in mg, of chlorpheniramine maleate (C
16H
19ClN
2 · C
4H
4O
4) in the portion of Tablets taken by the formula:
50C(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Chlorpheniramine Maleate RS in the
Chlorpheniramine standard preparation; and
rU and
rS are the peak responses obtained from the
Chlorpheniramine assay preparation and the
Chlorpheniramine standard preparation, respectively.
Assay for dextromethorphan hydrobromide (if present)
Dextromethorphan standard preparation
Dissolve an accurately weighed quantity of
USP Dextromethorphan Hydrobromide RS in water to obtain a solution having a known concentration of about 0.6 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 0.06 mg per mL.
Dextromethorphan assay preparation
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 3 mg of dextromethorphan hydrobromide, to a 50-mL volumetric flask. Add 5 mL of methanol, and sonicate to disperse the powder. Add 0.2 mL of phosphoric acid, dilute with water to volume, mix, and filter.
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 responses for the dextromethorphan peaks. Calculate the quantity, in mg, of dextromethorphan hydrobromide (C
18H
25NO·HBr·H
2O) in the portion of Tablets taken by the formula:
(370.33/352.32)50C(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; and
rU and
rS are the dextromethorphan peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.