A: The retention time of the diclofenac peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, as obtained in the Assay.

B: It meets the requirements of the flame test for Potassium 191.

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Medium: simulated intestinal fluid (without enzyme); 900 mL.

Apparatus 2: 50 rpm.

Time: 60 minutes.

Procedure— Determine the amount of C14H10Cl2KNO2 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 276 nm on portions of the solution under test passed through a 0.45-µm filter, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Diclofenac Potassium RS in the same Medium. Calculate the percentage of diclofenac potassium (C14H10Cl2KNO2) dissolved by the formula: in which AU and AS are the absorbances obtained from the solution under test and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg, of diclofenac potassium.

Tolerances— Not less than 75%4 (Q) of the labeled amount of C14H10Cl2KNO2 is dissolved in 60 minutes.

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Standard— Accurately transfer about 50.00 mg of potassium chloride into a fused quartz crucible.

Sample— Transfer not fewer than five diclofenac potassium 50-mg Tablets, accurately weighed, into a fused quartz crucible.

Blank— Prepare a dilution of 10% cesium chloride (1 in 50).

Test solutions— Place crucibles containing the Standard, Sample, and Blank in a muffle furnace at 550 for 8 hours to ash the contained material. Pipet 1.0 mL of concentrated hydrochloric acid and 1.0 mL of concentrated nitric acid into each cooled crucible. Heat each crucible on a hot plate to dissolve the residue. Transfer quantitatively, without filtering, the contents of each crucible to 100-mL volumetric flasks, and dilute with water to volume. Pipet 1.0 mL from each volumetric flask into separate 100-mL volumetric flasks, pipet 2.0 mL of 10% cesium chloride solution into each flask, and dilute with water to volume.

Procedure— Concomitantly determine the absorbances of the Test solutions and Blank at the potassium emission line at 766.5 nm with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering 851) equipped with an air–acetylene flame. Plot the absorbances of the Test solutions versus their potassium content. Calculate the weight percentage of potassium in each Tablet: not less than 2.40% and not more than 2.94% is found; and not less than 90.0% and not more than 110.0% of the calculated theoretical amount of potassium is found.4

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

Standard solution— Dissolve an accurately weighed quantity of USP Diclofenac Related Compound A RS in Diluent, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 2.5 µg per mL.4

Test solution— Use the Assay preparation.

Procedure— Separately inject equal volumes (about 30 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of diclofenac related compound A relative to the diclofenac potassium labeled content4 in the portion of Tablets taken by the formula: in which 0.001 is a conversion coefficient from µg per mL to mg per mL; CA is the concentration, in µg per mL, of diclofenac related compound A in the Standard solution; CT is the concentration, in mg per mL, of diclofenac potassium in the Test solution, based on the label claim;4 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%4 of diclofenac related compound A is found. Calculate the percentage of each of the other impurities, other than diethyl phthalate, if present, relative to the diclofenac potassium labeled content4 in the portion of Tablets taken by the formula: in which ri is the response of an individual impurity peak obtained from the Test solution, and the other terms are as defined above: not more than 0.5%4 of each individual impurity is found, and not more than 1.5%4 of total impurities is found.

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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 components to a pH of 2.5 ± 0.2.

Mobile phase— Prepare a filtered and degassed mixture of methanol and pH 2.5 Phosphate buffer (70:30). Make adjustments if necessary (see System Suitability under Chromatography 621).

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

Standard preparation— Dissolve an accurately weighed quantity of USP Diclofenac Potassium RS in Diluent, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.5 mg per mL.4

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 50 mg of diclofenac potassium, to a 100-mL volumetric flask. Add about 70 mL of Diluent, stir for 60 minutes, dilute with Diluent to volume, mix, and centrifuge.

Resolution solution— Prepare a solution in Diluent containing 40 µg per mL of diethyl phthalate, 0.5 mg per mL of USP Diclofenac Potassium RS, and 37.5 µg per mL of USP Diclofenac Potassium Related Compound A RS.

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 5-µm packing L7. The flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between diethyl phthalate and diclofenac related compound A is not less than 2.5, and the resolution, R, between diclofenac related compound A and diclofenac is not less than 3.5. 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 responses for the major peaks. Calculate the percentage of the labeled amount4 of diclofenac potassium (C14H10Cl2KNO2) in the portion of the Tablets4 taken by the formula: in which CS is the concentration, in mg per mL, of diclofenac potassium in the Standard preparation; CU is the concentration, in mg per mL, of diclofenac potassium in the Assay preparation, based on the label claim;4 and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.