A: Transfer the finely ground contents of 1 Tablet to a test tube, 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, about 65 mg of USP Aspirin RS and 20 mg of USP Propoxyphene Napsylate RS. Apply 10 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 10 µL of the Standard solution separately on the starting line. Place the plate in a developing chamber containing a mixture of chloroform, butyl acetate, 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 solution under test exhibits two principal spots having intensities and RF values identical to those of the two principal spots obtained from the Standard solution.

B: The Assay preparation prepared as directed in the Assay is dextrorotatory.

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.

Determination of dissolved propoxyphene napsylate—

Internal standard solution and pH 9.0 buffer—Prepare as directed in the test for Dissolution under Propoxyphene Hydrochloride, Aspirin, and Caffeine Capsules.

Standard preparation and Procedure—Proceed as directed in the test for Dissolution under Propoxyphene Napsylate Tablets.

Determination of dissolved aspirin— Proceed as directed for Determination of dissolved aspirin in the test for Dissolution under Propoxyphene Hydrochloride, Aspirin, and Caffeine Capsules.

Tolerances— Not less than 75% (Q) of the labeled amount of C22H29NO2·C10H8O3S·H2O and not less than 75% (Q) of the labeled amount of C9H8O4 are dissolved in 60 minutes.

Ferric chloride-urea reagent— Dissolve by swirling, without the aid of heat, 60 g of urea in a mixture of 8 mL of ferric chloride solution (6 in 10) and 42 mL of 0.05 N hydrochloric acid. Adjust this solution by the addition of 6 N hydrochloric acid to a pH of 3.2, if necessary.

Standard preparation— Transfer 15.0 mg of USP Salicylic Acid RS, accurately weighed, to a 100-mL volumetric flask, add chloroform to volume, and mix. Transfer 10.0 mL of this solution to a 100-mL volumetric flask containing 20 mL of methanol, 4 drops of hydrochloric acid, and 20 mL of a 1 in 10 solution of glacial acetic acid in ether, dilute with chloroform to volume, and mix.

Test preparation— Pack a pledget of glass wool in the base of a 25- × 200-mm chromatographic tube. In a beaker, prepare a mixture of 6 g of chromatographic siliceous earth, 2 mL of freshly prepared Ferric chloride-urea reagent, and 40 mL of chloroform. Transfer the mixture to the chromatographic tube. Rinse the beaker with 15 mL of chloroform, transfer to the column, and pack tightly. Place a small amount of glass wool at the top of the column. Weigh accurately a quantity of the finely powdered contents of Tablets, equivalent to about 50 mg of aspirin, mix with 10 mL of chloroform by stirring for 3 minutes, and transfer with the aid of 10 mL of chloroform to the chromatographic column. Pass 40 mL of chloroform through the column, rinse the tip of the chromatographic tube with chloroform, and discard the eluate. Prepare as a receiver a 100-mL volumetric flask containing 20 mL of methanol and 4 drops of hydrochloric acid, and elute any salicylic acid from the column by passing 20 mL of a 1 in 10 solution of glacial acetic acid in ether that recently has been saturated with water, followed by 30 mL of chloroform. Dilute the eluate with chloroform to volume, and mix.

Procedure— Concomitantly determine the absorbances of the Standard preparation and the Test preparation in 1-cm cells at the wavelength of maximum absorbance at about 306 nm, with a suitable spectrophotometer, using as the blank a solvent mixture of the same composition as that used for the Standard preparation: the absorbance of the Test preparation does not exceed that of the Standard preparation (3.0%, calculated on the basis of the labeled content of aspirin).

(Official January 1, 2007)

Internal standard solution— Dissolve n-tricosane in chloroform to obtain a solution containing about 0.6 mg per mL.

Standard preparation— Transfer 50 mg of USP Propoxyphene Napsylate RS and 163 mg of USP Aspirin RS, all accurately weighed, to a 50-mL volumetric flask. Add 10 mL of acetone, and swirl to dissolve the Reference Standards completely. Dilute with water to volume, and mix.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of propoxyphene napsylate, to a 100-mL volumetric flask containing 20 mL of acetone, and sonicate for about 1 minute. Dilute the milky solution with water to volume, mix, and filter, discarding the first 20 mL of the filtrate.

Procedure— Transfer 5.0-mL aliquots of the Assay preparation and the Standard preparation to separate 60-mL separators. To each add 5.0 mL of sodium carbonate solution (1 in 5) and 5.0 mL of Internal standard solution. Shake vigorously for 5 minutes, and allow the layers to separate. Drain the chloroform layer through phase-separating paper, suitably supported in a funnel, into a screw-capped test tube. Extract with one 5-mL portion of chloroform, and drain the chloroform layer through phase-separating paper. Evaporate the combined chloroform extracts, using a stream of dry nitrogen, to a final volume of about 2 mL. Inject separately a suitable volume, equivalent to about 6.4 µg of propoxyphene, of the chloroform extracts from the Assay preparation and the Standard preparation into a suitable gas chromatograph equipped with a flame-ionization detector. The column is typically 120 cm × 3 mm and is packed with 3% phase G3 on support S1A. The temperature of the injection port is 200, the column temperature is 175, and the carrier gas is nitrogen flowing at the rate of about 60 mL per minute. Relative retention times are 1.0 for the internal standard, and 1.7 for propoxyphene. In a suitable chromatogram, the resolution factor is not less than 1.0 and the relative standard deviation for five replicate injections of the Standard preparation is not more than 2.0. Calculate the quantity, in mg, of C22H29NO2·C10H8O3S·H2O in the portion of Tablets taken by the formula: in which 565.72 and 547.72 are the molecular weights of propoxyphene napsylate monohydrate and anhydrous propoxyphene napsylate, respectively, C is the concentration, in mg per mL, of anhydrous propoxyphene napsylate in the Standard preparation, as determined from the concentration of USP Propoxyphene Napsylate RS corrected for moisture content by a titrimetric water determination, and RU and RS are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.

Sodium hydroxide reagent— Dissolve 1 g of polyoxyethylene (23) lauryl ether in about 100 mL of hot water contained in a 1000-mL volumetric flask. Dilute with water to about 600 mL, and dissolve 10 g of sodium hydroxide in this solution. Dilute with water to volume, and mix.

Ferric nitrate reagent— Mix 70 mL of nitric acid with about 600 mL of water contained in a 1000-mL volumetric flask. Dissolve 40 g of ferric nitrate [Fe(NO3)3·9H2O] in this solution, dilute with water to volume, and mix.

Standard preparation and Assay preparation—Prepare as directed in the Assay for propoxyphene napsylate.

Procedure— Into separate 25-mL volumetric flasks pipet 2 mL each of the Standard preparation and the Assay preparation, and 2 mL of dilute acetone (2 in 10) to provide the blank. Into each flask pipet 5 mL of Sodium hydroxide reagent, mix by gentle swirling, and allow to stand at room temperature for 8 minutes. Dilute with Ferric nitrate reagent to volume, and mix. Concomitantly determine the absorbances of both solutions against the blank in 1-cm cells at the wavelength of maximum absorbance at about 530 nm, taking care to allow the solutions to reach an equilibrium temperature in the cell compartment. The color intensity is temperature-dependent. Calculate the quantity, in mg, of C9H8O4 in the portion taken for the Assay preparation by the formula: in which C is the concentration, in mg per mL, of USP Aspirin RS in the Standard preparation, and AU and AS are the absorbances of the solutions from the Assay preparation and Standard preparation, respectively.