Identification—
Transfer 1 finely ground Tablet to a test tube. If the Tablets are coated, first immerse the Tablet in acetone for 1½ minutes, remove the shell, and grind. Add 5 mL of methanol, shake for 5 minutes, and centrifuge. Use the clear supernatant as the
Test solution. Prepare a
Standard solution in methanol containing, in each mL, 130 mg of
USP Acetaminophen RS and 13 mg of
USP Propoxyphene Hydrochloride RS. Apply 5 µL of the
Test solution on a line parallel to and about 2 cm from the bottom edge of a 20- × 5-cm thin-layer chromatographic plate (see
Chromatography 
621
) coated with chromatographic silica gel mixture, and apply 5 µL of the
Standard solution separately on the starting line. Place the plate in a developing chamber containing a mixture of butyl acetate, chloroform, and formic acid (60:40:20), and develop the chromatogram until the solvent front has moved about 15 cm above the line of application. Remove the plate, allow to dry in a hood, and view under short-wavelength UV light: the
RF value of the principal spot from the
Test solution corresponds to that from the
Standard solution. Spray the plate with
iodoplatinate TS: the
RF value of the orange-brown spot from the
Test solution corresponds to that from the
Standard solution.
Dissolution, Procedure for a Pooled Sample 711—
Medium: pH 4.5 acetate buffer,
prepared as directed in the test for
Dissolution under
Propoxyphene Hydrochloride,
Aspirin and Caffeine Capsules; 700 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Procedure—
Proceed as directed in the
Assay, using a filtered portion of the solution under test, diluted with
Mobile phase, and a Standard solution having accurately known concentrations of
USP Propoxyphene Hydrochloride RS and
USP Acetaminophen RS in
Mobile phase. Calculate the amounts of propoxyphene hydrochloride (C
22H
29NO
2·HCl) and acetaminophen (C
8H
9NO
2) dissolved.
Tolerances—
Not less than 80% (Q) of the labeled amount of C22H29NO2·HCl and not less than 80% (Q) of the labeled amount of C8H9NO2 are dissolved in 30 minutes.
Assay—
Mobile phase—
Mix 0.15% diethylamine in water, adjusted with phosphoric acid to a pH of 3.2 ± 0.2, and acetonitrile (4:1). Sonicate for 15 minutes, and filter through a filter having a porosity of 0.5 µm or finer. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation 1—
Transfer about 2
J mg of
USP Acetaminophen RS, accurately weighed, to a 10-mL volumetric flask,
J being the ratio of the labeled amount, in mg, of acetaminophen to the labeled amount, in mg, of propoxyphene hydrochloride in each Tablet. Transfer about 2 mg of
USP Propoxyphene Hydrochloride RS, accurately weighed, to the same flask. Add about 5 mL of
Mobile phase, swirl to dissolve, dilute with
Mobile phase to volume, and mix. This solution contains about 0.2 mg of
USP Propoxyphene Hydrochloride RS and 0.2
J mg of
USP Acetaminophen RS per mL.
Standard preparation 2—
Transfer 5.0 mL of
Standard preparation 1 to a 100-mL volumetric flask, dilute with
Mobile phase to volume, and mix. This solution contains about 0.01
J mg of
USP Acetaminophen RS per mL.
Assay preparation 1—
Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 40 mg of propoxyphene hydrochloride, to a 200-mL volumetric flask, add about 150 mL of Mobile phase, shake by mechanical means for 30 minutes, sonicate for 5 minutes, dilute with Mobile phase to volume, mix, and filter, discarding the first 20 mL of the filtrate. Use the clear filtrate as Assay preparation 1.
Assay preparation 2—
Transfer 5.0 mL of Assay preparation 1 to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system
(see
Chromatography 621)—The liquid chromatograph is equipped with a 210-nm detector and a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph
Standard preparation 1, and record the responses as directed for
Procedure: the tailing factor for the propoxyphene peak is not more than 2.0, and the relative standard deviation for replicate injections is not more than 2.0%. Chromatograph
Standard preparation 2, and record the responses as directed for
Procedure: the tailing factor for the acetaminophen peak is not more than 1.5, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
[NOTE—Use peak areas where peak responses are indicated.
] Separately inject equal volumes (about 20 µL) of
Standard preparation 1,
Standard preparation 2,
Assay preparation 1, and
Assay preparation 2 into the chromatograph, record the chromatograms using both the 210-nm and the 254-nm detectors, and measure the responses for the propoxyphene hydrochloride peaks obtained using the 210-nm detector and for the acetaminophen peaks obtained using the 254-nm detector. Calculate the quantity, in mg, of propoxyphene hydrochloride (C
22H
29NO
2·HCl) in the portion of Tablets taken by the formula:
200C(rU / rS),
in which
C is the concentration, in µg per mL, of
USP Propoxyphene Hydrochloride RS in
Standard preparation 1, and
rU and
rS are the propoxyphene hydrochloride peak responses obtained from
Assay preparation 1 and
Standard preparation 1, respectively. Calculate the quantity, in mg, of acetaminophen (C
8H
9NO
2) in the portion of Tablets taken by the formula:
4000C(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Acetaminophen RS in
Standard preparation 2, and
rU and
rS are the acetaminophen peak responses obtained from
Assay preparation 2 and
Standard preparation 2, respectively.
