Limit of amphetamine hydrochloride and phenylpropanediol—
Mobile phase—
Prepare a mixture of 20 mL of 10% tetramethylammonium hydroxide and 5 mL of phosphoric acid, dilute with water to a volume of 1000 mL, and mix. To 896 mL of the resulting solution add 100 mL of methanol, 4 mL of tetrahydrofuran, and mix. Filter and degas the mixture. Make adjustments if necessary (see
System Suitability under
Chromatography 
621
).
Standard solution B—
Dissolve an accurately weighed quantity of
USP Phenylpropanediol RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.1 mg per mL.
Test solution—
Transfer about 1000 mg of Phenylpropanolamine Bitartrate, accurately weighed, to a 10-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system
(see
Chromatography 621)—The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 15-cm column that contains spherical 5-µm packing L1. The flow rate is about 2.0 mL per minute. Separately chromatograph the
Resolution solution and each
Standard solution, and record the peak responses as directed for
Procedure: the relative retention times are about 1.0 for phenylpropanolamine, between 1.9 and 2.1 for dextroamphetamine, and between 2.3 and 2.7 for phenylpropanediol; the resolution,
R, between phenylpropanolamine and dextroamphetamine in the chromatogram of the
Resolution solution is not less than 5.0; and the relative standard deviation for replicate injections of the
Standard solutions is not more than 3.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of
Standard solution A,
Standard solution B, and the
Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of phenylpropanediol in the portion of Phenylpropanolamine Bitartrate taken by the formula:
1000C / W(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Phenylpropanediol RS in
Standard solution B; W is the weight, in mg, of Phenylpropanolamine Bitartrate taken to prepare the
Test solution; and
rU and
rS are the peak responses obtained from the
Test solution and the
Standard solution B, respectively. The limit of phenylpropanediol is not more than 0.2%.
Calculate the percentage of amphetamine hydrochloride in the portion of Phenylpropanolamine Bitartrate taken by the formula:
(343.34 / 368.49)(C / W)(rU / rS),
in which 343.34 is twice the molecular weight of amphetamine hydrochloride; 368.49 is the molecular weight of dextroamphetamine sulfate;
C is the concentration, in µg per mL, of
USP Dextroamphetamine Sulfate RS in
Standard solution A; W is the weight, in mg, of Phenylpropanolamine Bitartrate taken to prepare the
Test solution; and
rU and
rS are the amphetamine peak responses obtained from the
Test solution and
Standard solution A, respectively. The limit of amphetamine hydrochloride is not more than 0.001%.
Assay—
Dissolve about 500 mg of Phenylpropanolamine Bitartrate, previously dried and accurately weighed, in 50 mL of glacial acetic acid. Add 10 mL of
mercuric acetate TS and 2 drops of
crystal violet TS, and titrate with 0.1 N perchloric acid VS to a green endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 30.13 mg of C
9H
13NO·C
4H
6O
6.
-(1-Aminoethyl)benzenemethanol bitartrate
for 3 hours: it loses not more than 1.0% of its weight.