Ibuprofen

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Ibuprofen

C₁₃H₁₈O₂  206.28

Benzeneacetic acid, α-methyl-4-(2-methylpropyl), (±)-.

(±)-p-Isobutylhydratropic acid.

(±)-2-(p-Isobutylphenyl)propionic acid

CAS RN®: 15687-27-1; UNII: WK2XYI10QM.

(±) Mixture CAS RN®: 58560-75-1.

» Ibuprofen contains not less than 97.0 percent and not more than 103.0 percent of C₁₃H₁₈O₂, calculated on the anhydrous basis.

Packaging and storage—

Preserve in tight containers.

USP Reference standards 〈11〉—

USP Ibuprofen RS

USP Ibuprofen Related Compound C RS

1 Identification—

Change to read:

A: ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M▲ (CN 1-May-2020) — Do not dry specimens.

Change to read:

B: ▲Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U▲ (CN 1-May-2020)

Solution: 250 µg per mL.

Medium: 0.1 N sodium hydroxide.

Respective absorptivities at 264 nm and 273 nm, calculated on the anhydrous basis, do not differ by more than 3.0%.

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.

Water Determination, Method I 〈921〉: not more than 1.0%.

Residue on ignition 〈281〉: not more than 0.5%.

Chromatographic purity—

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 ± 0.5°. 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:

100rᵢ / rₜ

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%.

Limit of ibuprofen related compound C—

Using the chromatograms of the Assay preparation and the Ibuprofen related compound C standard solution, obtained as directed in the Assay, calculate the percentage of ibuprofen related compound C (C₁₂H₁₆O) in the portion of Ibuprofen taken by the formula:

10,000(C/W)(Rᵤ / Rₛ)

in which C is the concentration, in mg per mL, of USP Ibuprofen Related Compound C RS in the Ibuprofen related compound C standard solution;

W is the weight, in mg, of Ibuprofen taken to prepare the Assay preparation; and

Rᵤ and Rₛ are the peak response ratios of ibuprofen related compound C to valerophenone obtained from the Assay preparation and the Ibuprofen related compound C standard solution, respectively:

not more than 0.1% is found.

2 Assay—

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:

100C(Rᵤ / Rₛ)

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.