Ketoprofen

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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C₁₆H₁₄O₃ 254.28

Benzeneacetic acid, 3-benzoyl-α-methyl-, (±)-;

(±)-m-Benzoylhydratropic acid CAS RN®: 22071-15-4; UNII: 90Y4QC304K.

1 DEFINITION

Ketoprofen contains NLT 98.5% and NMT 101.0% of C₁₆H₁₄O₃ , calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Change to read:

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

Analytical wavelength: 258 nm

Medium: Methanol and water (3:1)

Blank: Medium

Sample solution: 10 μg/mL in Medium

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%.

3 ASSAY

Procedure

Sample: 450 mg

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N sodium hydroxide VS

Endpoint detection: Visual

Analysis: Dissolve the Sample in 25 mL of alcohol. Add 25 mL of water and several drops of phenol red TS. Perform a blank determination.

Each mL of Titrant is equivalent to 25.43 mg of C₁₆H₁₄O₃ . [Note—Standardize the 0.1 N sodium hydroxide by a similar titration of primary standard benzoic acid.]

Acceptance criteria: 98.5%–101.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Organic Impurities

[Note—Protect the solutions from light.]

Buffer: 68 g/L of monobasic potassium phosphate in water, and adjust with phosphoric acid to a pH of 3.5 ± 0.05

Mobile phase: Acetonitrile, water, and Buffer (43:55:2)

System suitability solution: 5 μg/mL of USP Ketoprofen RS and 1.5 μg/mL of USP Ketoprofen Related Compound D RS in Mobile phase

Standard solution: 0.002 mg/mL of USP Ketoprofen RS in Mobile phase

Sample solution: 1 mg/mL of Ketoprofen in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 233 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection size: 20 μL

Run time: Seven times the retention time for Ketoprofen

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for ketoprofen and ketoprofen related compound D (3-acetylbenzophenone) are about 1.0 and 1.6, respectively.]

Suitability requirements

Resolution: NLT 7.0 between ketoprofen related compound D and ketoprofen, System suitability solution Column efficiency: NLT 2250 theoretical plates from ketoprofen, System suitability solution

Tailing factor: NMT 2.0 for ketoprofen, System suitability solution

Relative standard deviation: NMT 5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Ketoprofen taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response of impurity from the Sample solution

r_S = peak response of ketoprofen from the Standard solution

C_S = concentration of USP Ketoprofen RS in the Standard solution (mg/mL)

C_U = concentration of the Sample solution (mg/mL)

Acceptance criteria

Any individual impurity: NMT 0.2%

Total impurities: NMT 1.0%

5 SPECIFIC TESTS

Melting Range or Temperature, Procedure for Class I〈741〉: 92.0°–97.0°

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 10 mg/mL, in dehydrated alcohol

Acceptance criteria: +1° to −1°

Loss on Drying 〈731〉: Dry a sample in a vacuum at 60° for 4 h: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Ketoprofen RS

USP Ketoprofen Related Compound D RS

3-Acetylbenzophenone.