Internal standard stock solution— Dissolve suitable quantities of isopropyl alcohol in dimethylformamide to obtain a solution containing about 2.5 µL per mL.

Internal standard solution— Pipet 5.0 mL of Internal standard stock solution into a 100-mL volumetric flask. Dilute with dimethylformamide to volume, and mix. This solution contains 0.125 µL of isopropyl alcohol.

Standard stock solution— Transfer 5.0 mL of methanol and 5.0 mL of alcohol to a 200-mL volumetric flask. Dilute with dimethylformamide to volume, and mix. Pipet 5.0 mL of this solution into a 100-mL volumetric flask, dilute with dimethylformamide to volume, and mix.

Standard solution— Pipet 10.0 mL of Standard stock solution and 5.0 mL of Internal standard stock solution into a 100-mL volumetric flask. Dilute with dimethylformamide to volume, and mix. This solution contains 0.101 mg of methanol and 0.099 mg of alcohol per mL.

Test solution— Transfer about 0.5 g of Etodolac, accurately weighed, to a 10-mL flask. Pipet 5.0 mL of Internal standard solution into the flask. Insert a stopper into the flask, and sonicate to dissolve.

Chromatographic system (see Chromatography 621)—The gas chromatograph is equipped with a flame-ionization detector and a 0.32-mm × 25-m fused silica capillary column coated with a 5-µm film of phase G36. The carrier gas is helium, with a split flow rate of 50 mL per minute. The injection port temperature is maintained at 200, and the detector is maintained at 300. The column temperature is maintained at 45 for 5 minutes, then programmed to increase at the rate of 30 per minute to 280 and to maintain this temperature for 27 minutes. Chromatograph the Standard solution and the Test solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.6 for methanol, 0.8 for alcohol, and 1.0 for isopropyl alcohol; and the resolution, R, between peaks is not less than 1.

Procedure— Separately inject equal volumes (about 1 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas of the peak responses. Identify by their retention times any peaks present in the chromatogram obtained from the Test solution that correspond to those in the chromatogram obtained from the Standard solution. Calculate the percentages of C2H5OH and CH3OH in the portion of Etodolac taken by the formula: in which C is the concentration, in mg per mL, of C2H5OH or CH3OH in the Standard solution; W is the weight, in mg, of Etodolac taken to prepare the Test solution; and RU and RS are the peak area ratios of the relevant analyte to the internal standard obtained from the Test solution and the Standard solution, respectively: not more than 0.1% of each is found.

Solution A— Mix 0.6 mL of phosphoric acid with 100 mL of water.

Solution B— Mix 0.6 mL of phosphoric acid with 100 mL of acetonitrile.

Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability solution— Dissolve suitable quantities of USP Etodolac Related Compound A RS and USP Etodolac RS in acetonitrile to obtain a solution containing about 0.01 mg per mL and 0.2 mg per mL, respectively.

Test solution— Transfer about 25 mg of Etodolac, accurately weighed, to a 250-mL volumetric flask, dissolve in and dilute with acetonitrile to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 214-nm detector and a 4-mm × 25-cm column that contains packing L7. The flow rate is about 1 mL per minute. The chromatograph is programmed as follows. 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 3; the tailing factor is not more than 2; and the relative standard deviation for replicate injections is not more than 3%.

Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of each impurity in the portion of Etodolac taken by the formula: in which ri is the peak response for each impurity; and rs is the sum of the responses of all of the peaks: not more than 0.5% of any individual impurity is found; and the total of all impurities is not more than 2.0%.

(Official January 1, 2007)