ACID STAGE—

Medium: 0.1 N hydrochloric acid; 900 mL.

Apparatus 2 (paddles constructed of, or coated with, polytef being used): 50 rpm.

Procedure— At the end of 2 hours, remove each Tablet, or the major portion thereof if the Tablet is not intact, from the individual vessels, and subject them to the test in the Buffer stage. To the 0.1 N hydrochloric acid remaining in each vessel, add 20.0 mL of 5 N sodium hydroxide, and stir for 5 minutes. Determine the amount of C14H10Cl2NNaO2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solution under test in comparison with a Standard solution prepared as follows. Transfer about 68 mg of USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 3.0 mL of this solution to a second 100-mL volumetric flask, dilute with a mixture of 0.1 N hydrochloric acid and 5 N sodium hydroxide (900:20) to volume, and mix. This Standard solution contains about 13.6 µg of USP Diclofenac Sodium RS per mL.

BUFFER STAGE—

pH 6.8 Phosphate buffer— Dissolve 76 g of tribasic sodium phosphate in water to obtain 1000 mL of solution. Mix 250 mL of this solution with 750 mL of 0.1 N hydrochloric acid, and, if necessary, adjust with 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 ± 0.05.

Medium: pH 6.8 Phosphate buffer; 900 mL.

Apparatus 2: 50 rpm.

Procedure— At the end of 45 minutes, determine the amount of C14H10Cl2NNaO2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solutions under test, suitably diluted with Medium, in comparison with a Standard solution prepared as follows. Transfer about 68 mg of USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 3.0 mL of this solution to a second 100-mL volumetric flask, dilute with Medium, as obtained in the Buffer stage, to volume, and mix. This Standard solution contains about 0.02 mg of USP Diclofenac Sodium RS per mL.

Tolerances— Not less than 75% (Q) of the labeled amount of C14H10Cl2NNaO2 is dissolved.

ACID STAGE—

Medium: 0.1 N hydrochloric acid; 900 mL.

Apparatus 2 (paddles constructed of, or coated with, polytef being used): 50 rpm.

Procedure— At the end of 2 hours, remove each Tablet, or the major portion thereof if the Tablet is not intact, from the individual vessels, and subject them to the test in the Buffer stage. To the 0.1 N hydrochloric acid remaining in each vessel, add 20.0 mL of 5 N sodium hydroxide, and stir for 5 minutes. Determine the amount of C14H10Cl2NNaO2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solution under test in comparison with a Standard solution prepared as follows. Transfer about 68 mg of USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 3.0 mL of this solution to a second 100-mL volumetric flask, dilute with a mixture of 0.1 N hydrochloric acid and 5 N sodium hydroxide (900:20) to volume, and mix. This Standard solution contains about 13.6 µg of USP Diclofenac Sodium RS per mL.

BUFFER STAGE—

pH 6.8 Phosphate buffer— Dissolve 76 g of tribasic sodium phosphate in water to obtain 1000 mL of solution. Mix 250 mL of this solution with 750 mL of 0.1 N hydrochloric acid, and, if necessary, adjust with 2 N hydrochloric acid or 2 N sodium hydroxide to a pH of 6.8 ± 0.05.

Medium: pH 6.8 Phosphate buffer; 900 mL.

Apparatus 2: 50 rpm.

Procedure— At the end of 45 minutes, determine the amount of C14H10Cl2NNaO2 dissolved from UV absorbances at the wavelength of maximum absorbance at about 276 nm on filtered portions of the solutions under test, suitably diluted with Medium, in comparison with a Standard solution prepared as follows. Transfer about 68 mg of USP Diclofenac Sodium RS, accurately weighed, to a 100-mL volumetric flask, add 10.0 mL of 0.1 N sodium hydroxide, dilute with water to volume, and mix. Transfer 3.0 mL of this solution to a second 100-mL volumetric flask, dilute with Medium, as obtained in the Buffer stage, to volume, and mix. This Standard solution contains about 0.02 mg of USP Diclofenac Sodium RS per mL.

Tolerances— Not less than 75% (Q) of the labeled amount of C14H10Cl2NNaO2 is dissolved.

(Official April 1, 2006)

pH 2.5 Phosphate buffer, Mobile phase, Diluent, Resolution solution, and Chromatographic system— Proceed as directed in the Assay.

Standard solution— Prepare a solution having a known concentration of about 0.8 mg per mL of USP Diclofenac Related Compound A RS in methanol. Dilute an accurately measured volume of this stock solution with Diluent to obtain a solution having a known concentration of about 4 µg per mL.

Test solution— Use the Assay preparation, prepared as directed in the Assay.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses over a period of 40 minutes. Calculate the percentage of diclofenac related compound A in relation to the quantity of diclofenac sodium in the Tablets taken by the formula: in which C is the concentration, in µg per mL, of USP Diclofenac Related Compound A RS in the Standard solution; A is the quantity, in mg, of diclofenac sodium (C14H10Cl2NNaO2) in the Tablets taken for the Assay, as determined in the Assay; and rU and rS are the diclofenac related compound A peak responses obtained from the Test solution and the Standard solution, respectively: not more than 0.5% is found. Calculate the percentage of each other impurity, other than diethyl phthalate, if present, in relation to the diclofenac sodium in the Tablets taken by the formula: in which ri is the peak response for each impurity obtained from the Test solution, and the other terms are as defined above: not more than 1.0% of any individual impurity is found, and not more than 1.5% of total impurities is found.

(Official January 1, 2007)

pH 2.5 Phosphate buffer— Mix equal volumes of 0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate. If necessary, adjust with additional portions of the appropriate component to a pH of 2.5 ± 0.2.

Mobile phase— Prepare a filtered and degassed mixture of methanol and pH 2.5 Phosphate buffer (700:300). Make adjustments if necessary (see System Suitability under Chromatography 621). [NOTE—Increasing the proportion of buffer increases resolution.]

Diluent— Prepare a mixture of methanol and water (70:30).

Standard preparation— Prepare a solution of USP Diclofenac Sodium RS in Diluent having a known concentration of about 0.75 mg per mL.

Resolution solution— Prepare a solution in Diluent containing 20 µg of diethyl phthalate, 7.5 µg of USP Diclofenac Related Compound A RS, and 0.75 mg of USP Diclofenac Sodium RS per mL.

Assay preparation— Transfer 20 Tablets to a volumetric flask of such capacity that when filled to volume, a concentration of about 0.75 mg of diclofenac sodium per mL is obtained. Add Diluent to about 70% of the capacity of the flask, and shake by mechanical means for not less than 30 minutes to disintegrate the Tablets. Cool to room temperature, dilute with Diluent to volume, and mix. Pass a portion of the solution through a filter having a 0.5-µm or finer porosity, and use the filtrate as the Assay preparation.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L7 (end-capped). The flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.5 for diethyl phthalate, 0.6 for diclofenac related compound A, and 1.0 for diclofenac; and the resolution, R, between diethyl phthalate and diclofenac related compound A is not less than 2.2, and between diclofenac related compound A and diclofenac is not less than 6.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: 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. Calculate the quantity, in mg, of diclofenac sodium (C14H10Cl2NNaO2) in each Tablet taken by the formula: in which C is the concentration, in mg per mL, of USP Diclofenac Sodium RS in the Standard preparation; V is the volume of the flask used, in mL; and rU and rS are the diclofenac peak responses obtained from the Assay preparation and the Standard preparation, respectively.