A: Transfer a volume of Oral Suspension, equivalent to about 200 mg of ibuprofen, to a separator containing about 10 mL of chloroform, and shake for about 1 minute. Allow the layers to separate, and pass the lower chloroform layer through a filter containing about 2 g of anhydrous sodium sulfate. Use the filtrate as the test solution. [NOTE—Retain a portion of this test solution for use in Identification test B.] Separately apply 10-µL portions of the test solution and of a Standard solution containing 20 mg per mL of USP Ibuprofen RS in chloroform to a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel and previously activated by heating at 105 for 30 minutes. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of n-hexane, butyl acetate, and glacial acetic acid (17:3:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, and dry in a current of cool air. Examine the chromatograms under short-wavelength UV light: the RF value of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.

B: Infrared Absorption 197K—Prepare the test specimen and the standard as follows. Evaporate about 20 drops of the test solution and the Standard solution retained from Identification test A to dryness in a current of air without heating.

Medium: pH 7.2 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions); 900 mL.

Apparatus 2: 50 rpm.

Time: 60 minutes.

Mobile phase and Chromatographic system— Proceed as directed in the Assay.

Internal standard solution— Prepare a solution of benzophenone in acetonitrile containing about 0.3 mg per mL.

Standard solution— Dissolve an accurately weighed quantity of USP Ibuprofen RS in Dissolution Medium to obtain a solution having a known concentration of about 0.011J mg per mL, J being the labeled quantity, in mg, of ibuprofen in each mL of the Oral Suspension. Mix 10.0 mL of this solution and 10.0 mL of the Internal standard solution, pass the mixture through a filter having a 0.5-µm or finer porosity, and use the filtrate as the Standard solution.

Test solution— Filter a portion of the solution under test. Mix 10.0 mL of the filtrate and 10.0 mL of the Internal standard solution, pass the mixture through a filter having a 0.5-µm or finer porosity, and use the filtrate as the Test solution.

Procedure— Using an accurately tared syringe, draw about 10 mL of well-mixed Oral Suspension into the syringe, which is connected to tubing, and accurately weigh. [NOTE—The tubing of the syringe is placed into a zone that is between the surface of the Dissolution Medium and the top of the rotating blade.] Express the Oral Suspension into the Dissolution Medium. Promptly reweigh the syringe, and determine the weight, WU, in g, of the Oral Suspension added to the Dissolution Medium. Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the percentage of the labeled amount of C13H18O2 dissolved by the formula: in which C is the concentration, in mg per mL, of USP Ibuprofen RS in the Standard solution; L is the labeled quantity, in mg per mL, of ibuprofen in the Oral Suspension; D is the density, in g per mL, of the Oral Suspension, determined as directed for Density in the Assay; WU is the weight, in g, of the Oral Suspension added to the Dissolution Medium; and RU and RS are the ratios of the ibuprofen peak areas to the benzophenone peak areas obtained from the Test solution and the Standard solution, respectively.

Tolerances— Not less than 80% (Q) of the labeled amount of C13H18O2 is dissolved in 60 minutes.

FOR ORAL SUSPENSION PACKAGED IN SINGLE-UNIT CONTAINERS: meets the requirements.

FOR ORAL SUSPENSION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.

Mobile phase and Diluent— Proceed as directed in the Assay.

Standard solution— Quantitatively dissolve an accurately weighed quantity of 4-isobutylacetophenone in acetonitrile to obtain a stock solution having a known concentration of about 0.5 mg per mL. Transfer 3.0 mL of this stock solution to a 50-mL volumetric flask, dilute with Diluent to volume, and mix. Transfer 2.0 mL of this solution to a second 50-mL volumetric flask, add 18 mL of Diluent, dilute with acetonitrile to volume, mix, and pass through a filter having a porosity of 0.22 µm. This Standard solution contains about 0.0012 mg of 4-isobutylacetophenone per mL.

Test solution— Transfer 20.0 mL of the portion of the stock solution retained from the Assay preparation in the Assay into a 50-mL volumetric flask, dilute with acetonitrile to volume, mix, and pass through a filter having a 0.22-µm porosity.

System suitability solution— Transfer 1.5 mL of the stock solution of 4-isobutylacetophenone prepared as directed for Standard solution and 9 mL of the stock solution of USP Ibuprofen RS prepared as directed for Standard preparation in the Assay to a 25-mL volumetric flask, dilute with acetonitrile to volume, mix, and pass through a filter having a 0.22-µm porosity. This solution contains about 0.03 mg of 4-isobutylacetophenone and about 0.4 mg of USP Ibuprofen RS per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 2 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.3 for 4-isobutylacetophenone and 1.0 for ibuprofen; the tailing factor is not more than 2.0; and the resolution, R, between ibuprofen and 4-isobutylacetophenone is not less than 1.5. Chromatograph the Standard solution, 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 35 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the percentage of 4-isobutylacetophenone in the Oral Suspension, based on the labeled content of ibuprofen, taken by the formula: in which C is the concentration, in mg per mL, of 4-isobutylacetophenone in the Standard solution; D is the quantity, in mL, of Oral Suspension taken to prepare the stock solution for the Assay preparation; L is the labeled quantity, in mg, of ibuprofen in each mL of Oral Suspension; and rU and rS are the 4-isobutylacetophenone peak areas obtained from the Test solution and the Standard solution, respectively. Not more than 0.25% is found.

(Official January 1, 2007)

Mobile phase— Dilute 0.7 mL of phosphoric acid with water to obtain 1000 mL of 0.01 M phosphoric acid. Prepare a mixture of this solution and acetonitrile (63:37). Make adjustments if necessary (see System Suitability under Chromatography 621).

Diluent— Prepare a mixture of acetonitrile and water (1:1).

Internal standard solution— Prepare a solution of benzophenone in acetonitrile containing about 3.2 mg per mL.

Standard preparation— Quantitatively dissolve an accurately weighed quantity of USP Ibuprofen RS in Diluent to obtain a stock solution having a known concentration of about 1.2 mg per mL. Transfer 20.0 mL of this stock solution and 5.0 mL of Internal standard solution to a 50-mL volumetric flask, dilute with acetonitrile to volume, mix, and filter. This solution contains about 0.48 mg of USP Ibuprofen RS per mL.

Density— Using a tared 50-mL volumetric flask, weigh 50 mL of Oral Suspension that has been previously well shaken to ensure homogeneity, allow to stand until the entrapped air has risen, and finally invert carefully just prior to transferring it to the volumetric flask. From the observed weight of 50 mL of the Oral Suspension, calculate the density, in g per mL, of the Oral Suspension.

Assay preparation— Transfer an accurately weighed portion of Oral Suspension, equivalent to about 60 mg of Ibuprofen, to a 50-mL volumetric flask, dilute with Diluent to volume, and mix (stock solution). Transfer 20.0 mL of this stock solution and 5.0 mL of Internal standard solution to a second 50-mL volumetric flask, dilute with acetonitrile to volume, mix, and filter. [NOTE—Retain a portion of the stock solution for use in the test for Limit of 4-isobutylacetophenone.]

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for benzophenone and 1.0 for ibuprofen; the resolution, R, between benzophenone and ibuprofen is not less than 1.5; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C32H18O2 in each mL of the Oral Suspension taken by the formula: in which C is the concentration, in mg per mL, of USP Ibuprofen RS in the Standard preparation; D is the density, in g per mL, of Oral Suspension; WU is the weight, in g, of the portion of Oral Suspension taken to prepare the Assay preparation; and RU and RS are the ratios of the ibuprofen peak areas to the benzophenone peak areas obtained from the Assay preparation and the Standard preparation, respectively.