Identification—
Transfer an accurately weighed quantity of Capsule contents remaining from the preparation of the
Assay preparation in the
Assay, equivalent to about 320 mg of propoxyphene hydrochloride, to a 100-mL volumetric flask. Add 20 mL of acetone, and sonicate for about 1 minute. Dilute the solution with water to volume, and mix. Allow to stand until the excipients have settled, usually about 15 to 20 minutes. Transfer 40.0 mL of this solution to a 125-mL separator containing 20 mL of sodium carbonate solution (1 in 10), and swirl the mixture for 3 minutes. Add 25.0 mL of chloroform, insert the stopper, and shake the mixture by mechanical means for 1 hour. Filter the chloroform extract through a layer of anhydrous sodium sulfate into a suitable beaker. Prepare a Standard solution as follows. Transfer about 125 mg of
USP Propoxyphene Hydrochloride RS, accurately weighed, to a 125-mL separator containing 8 mL of acetone, 32 mL of water, and 20 mL of sodium carbonate solution (1 in 10), and swirl the mixture for 3 minutes. Proceed as directed for the test solution, beginning with “Add 25.0 mL of chloroform.” Use the chloroform solutions obtained from the Capsule contents and from the
USP Propoxyphene Hydrochloride RS for the following tests.
A:
The IR absorption spectrum of the chloroform solution of the contents of Capsules, concentrated if necessary by evaporating a portion on a steam bath with the aid of a current of air to about one-fifth of its volume, exhibits maxima only at the same wavelengths as that of a similar preparation of
USP Propoxyphene Hydrochloride RS.
B:
Transfer 20.0 mL of the test solution and 20.0 mL of the Standard solution to separate beakers, and evaporate on a steam bath with the aid of a current of air to about 5 mL. Remove the beakers from the steam bath, and continue evaporation with the aid of a current of air until the chloroform is completely evaporated. Add 5.0 mL of 0.1 N hydrochloric acid to each, and dissolve the residue. Using the solution obtained from the test solution, determine the specific rotation (see
Optical Rotation 
781
), in which
c, the concentration of propoxyphene hydrochloride per 100 mL of solution, is calculated as follows:
0.0064(WU / WT)A,
in which
WU is the weight, in mg, of the portion of Capsule contents taken,
WT is the average weight, in mg, of the contents of each Capsule, and
A is the quantity, in mg, of propoxyphene hydrochloride per Capsule, as obtained in the
Assay. Using the solution obtained from the Standard solution, determine the specific rotation,
c, being calculated by multiplying the weight, in mg, of
USP Propoxyphene Hydrochloride RS taken by 0.016. The specific rotation obtained from the solution from the test solution is not less than 95.0% of that obtained from the solution from the Standard solution.
C:
The chromatogram of the
Assay preparation obtained as directed in the
Assay exhibits a major peak for propoxyphene hydrochloride, the retention time of which corresponds to that exhibited in the chromatogram of the
Standard preparation obtained as directed in the
Assay.
Dissolution 711—
Medium: pH 4.5 acetate buffer
, prepared as directed in the test for
Dissolution under
Propoxyphene Hydrochloride,
Aspirin,
and Caffeine Capsules; 500 mL.
Apparatus 1:
100 rpm.
Time:
60 minutes.
Procedure—
Proceed as directed in the
Assay using a filtered portion of the solution under test diluted with
Diluent, and a Standard solution having an accurately known concentration of
USP Propoxyphene Hydrochloride RS in
Diluent. Calculate the amount of propoxyphene hydrochloride dissolved.
Tolerances—
Not less than 85% (Q) of the labeled amount of C22H29NO2·HCl is dissolved in 60 minutes.
Assay—
Phosphate buffer—
Dissolve 6.8 g of monobasic potassium phosphate in about 900 mL of water. Add 2.0 mL of triethylamine, mix, and adjust by the addition of phosphoric acid to a pH of 3.0 ± 0.1. Dilute with water to 1 liter, and mix.
Diluent—
Prepare a mixture of water and acetonitrile (3:2).
Mobile phase—
Prepare a filtered and degassed mixture of
Phosphate buffer and acetonitrile (3:2). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation—
Dissolve an accurately weighed quantity of
USP Propoxyphene Hydrochloride RS in
Diluent with the aid of sonication to obtain a solution having a known concentration of about 325 µg per mL. Transfer 2.0 mL of this solution to a 100-mL volumetric flask, dilute with
Diluent to volume, and mix to obtain a
Standard preparation having a known concentration of about 6.5 µg per mL.
Assay preparation—
Remove, as completely as possible, the contents of not less than 20 Capsules. Weigh the contents, and determine the average weight per capsule. Mix the combined contents, and transfer an accurately weighed quantity of the powder, equivalent to about 65 mg of propoxyphene hydrochloride, to a 200-mL volumetric flask. Add about 50 mL of Diluent, sonicate for 5 minutes, and shake by mechanical means for 15 minutes. Dilute with Diluent to volume, mix, and filter, discarding the first 20 mL of the filtrate. Transfer 2.0 mL of the filtrate to a 100-mL volumetric flask, dilute with Diluent to volume, and mix.
Chromatographic system
(see
Chromatography 621)—The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 3.3-cm column that contains 3-µm packing L1 that is base-deactivated. Precondition the column for at least 30 minutes with
Mobile phase. 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 propoxyphene hydrochloride peak is not more than 2, 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 peak responses for the major peaks. Calculate the quantity, in mg, of C
22H
29NO
2·HCl in the portion of Capsules taken by the formula:
10C(rU / rS),
in which
C is the concentration, in µg per mL, of
USP Propoxyphene Hydrochloride RS in the
Standard preparation, and
rU and
rS are the propoxyphene hydrochloride peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
