Medium: 0.05 M phosphate buffer, pH 7.4; 1000 mL.

Apparatus 2: 75 rpm, with sinker.

Times: 3, 6, 10, and 16 hours.

Procedure— Determine the amount of C17H21NO3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 279 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Etodolac RS in the same Medium. Use Medium as the blank.

Tolerances— The percentages of the labeled amount of C17H21NO3 dissolved at the times specified conform to Acceptance Table 1.

Diluent, Mobile phase, and System suitability solution— Proceed as directed in the Assay.

Test solution— Use the Assay preparation.

Chromatographic system— Prepare as directed in the Assay. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for etodolac related compound A and 1.0 for etodolac; the resolution, R, between etodolac related compound A and etodolac is not less than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure all of the peak areas. Calculate the percentage of each impurity in the portion of Tablets taken by the formula: in which ri is the peak area for each impurity, and rS is the sum of the areas of all the peaks: not more than 0.2% of any individual impurity is found; and not more than 0.75% of total impurities is found.

(Official January 1, 2007)

Diluent— Use acetonitrile.

Mobile phase— Prepare a filtered and degassed mixture of acetonitrile, water, and phosphoric acid (500:500:0.25). Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability solution— Dissolve accurately weighed quantities of USP Etodolac RS and USP Etodolac Related Compound A RS in Diluent, and quantitatively dilute with Diluent to obtain a solution having known concentrations of about 0.48 mg per mL and 0.05 mg per mL, respectively.

Standard preparation— Dissolve an accurately weighed quantity of USP Etodolac RS in Diluent, and quantitatively dilute with Diluent to obtain a solution having a known concentration of about 0.6 mg per mL.

Assay preparation— [NOTE—Do not finely powder Tablets.] Weigh and powder not fewer than 20 Tablets, and transfer an accurately weighed portion of the powder, equivalent to about 600 mg of etodolac, to a 200-mL volumetric flask. Add about 100 mL of Diluent, mix, and shake for 40 minutes by mechanical means. Dilute with Diluent to volume, and mix. Pass through a filter having a 0.45-µm porosity, discarding the first 3 mL of the filtrate. Transfer 2.0 mL of the filtrate to a 10-mL volumetric flask, dilute with Diluent to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 274-nm detector, a 4.0-mm × 4.0-cm guard column that contains 5-µm packing L1, and a 4.0-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for etodolac related compound A and 1.0 for etodolac; the resolution, R, between etodolac related compound A and etodolac is not less than 2.5; and the tailing factor is not more than 2.0. 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 quantity, in mg, of etodolac (C17H21NO3) in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Etodolac RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.