A: Infrared Absorption 197M—Do not dry specimens.

B: Ultraviolet Absorption 197U—

C: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a major peak for ibuprofen, the retention time of which, relative to that of the internal standard, corresponds to that exhibited in the chromatogram of the Standard preparation, obtained as directed in the Assay.

Mobile phase— Prepare a suitable filtered mixture of water, previously adjusted with phosphoric acid to a pH of 2.5 and acetonitrile (1340:680). Make adjustments if necessary (see System Suitability under Chromatography 621).

Test preparation— Prepare a solution of Ibuprofen in acetonitrile containing about 5 mg per mL.

Resolution solution— Prepare a solution in acetonitrile containing in each mL about 5 mg of Ibuprofen and 5 mg of valerophenone.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 214-nm detector and a 4-mm × 15-cm column that contains 5-µm packing L1 and is maintained at 30 ± 0.2. The flow rate is about 2 mL per minute. Chromatograph a series of 5-µL injections of the Test preparation to condition the column. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for valerophenone and 1.0 for ibuprofen, and the resolution, R, between the valerophenone peak and the ibuprofen peak is not less than 2.0.

Procedure— [note—Use peak areas where peak responses are indicated.] Inject about 5 µL of the Test preparation into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of each impurity taken by the formula: in which ri is the response of an individual peak, other than the solvent peak and the main ibuprofen peak, and rt is the sum of the responses of all the peaks, excluding that of the solvent peak: not more than 0.3% of any individual impurity is found, and the sum of all the individual impurities found does not exceed 1.0%.

10,000(C / W)(RU / RS)

Mobile phase— Dissolve 4.0 g of chloroacetic acid in 400 mL of water, and adjust with ammonium hydroxide to a pH of 3.0. Add 600 mL of acetonitrile, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

Internal standard solution— Prepare a solution of valerophenone in Mobile phase having a concentration of about 0.35 mg per mL.

Standard preparation— Dissolve an accurately weighed quantity of USP Ibuprofen RS in Internal standard solution to obtain a solution having a known concentration of about 12 mg per mL.

Ibuprofen related compound C standard solution— Quantitatively dissolve an accurately weighed quantity of USP Ibuprofen Related Compound C RS in acetonitrile to obtain a solution having a known concentration of about 0.6 mg per mL. Add 2.0 mL of this stock solution to 100.0 mL of Internal standard solution, and mix to obtain a solution having a known concentration of about 0.012 mg of ibuprofen related compound C per mL.

Assay preparation— Transfer about 1200 mg of Ibuprofen, accurately weighed, to a 100-mL volumetric flask, dilute with Internal standard solution to volume, and mix.

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 L1. 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 1.4 for the internal standard and 1.0 for ibuprofen; the resolution, R, between ibuprofen and the internal standard is not less than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%. Chromatograph the Ibuprofen related compound C standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for valerophenone and 1.2 for ibuprofen related compound C; the resolution, R, between valerophenone and ibuprofen related compound C is not less than 2.5; the tailing factors for the individual peaks are not more than 2.5; 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, the Assay preparation, and the Ibuprofen related compound C standard solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C13H18O2 in the portion of Ibuprofen taken by the formula: in which C is the concentration, in mg per mL, of USP Ibuprofen RS in the Standard preparation; and RU and RS are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.