Ketoprofen Capsules

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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1 DEFINITION

Ketoprofen Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of ketoprofen (C₁₆H₁₄O₃).

2 IDENTIFICATION

Change to read:

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

Sample solution: Shake a quantity of the contents of the Capsules containing 50 mg of ketoprofen with 5 mL of chloroform for 5 min, filter, and evaporate to dryness using a rotary evaporator.

Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

The Standard solution and Sample solution must be protected from light.

Mobile phase: Acetonitrile, glacial acetic acid, and water (90:1:110)

System suitability stock solution: 0.25 mg/mL of USP Ketoprofen RS and 0.5 mg/mL of USP Ketoprofen Related Compound A RS in Mobile phase

System suitability solution: 0.02 mg/mL of USP Ketoprofen RS and 0.04 mg/mL of USP Ketoprofen Related Compound A RS in Mobile phase from System suitability stock solution

Standard stock solution: 0.24 mg/mL of USP Ketoprofen RS in Mobile phase

Standard solution: 0.024 mg/mL of USP Ketoprofen RS in Mobile phase from Standard stock solution

Sample solution: Nominally 0.024 mg/mL of ketoprofen in Mobile phase prepared as follows. Remove completely the contents of NLT 20

Capsules, and transfer a quantity of the contents, equivalent to 200 mg of ketoprofen, to a 250-mL volumetric flask. Add 150 mL of Mobile phase, stir for 2 h, then dilute with Mobile phase to volume. Centrifuge a portion of the preparation. Pipet 3.0 mL of clear supernatant into a 100-mL volumetric flask. Dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.2 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3.0 between ketoprofen and ketoprofen related compound A, System suitability solution

Tailing factor: NMT 1.5 for the ketoprofen peak, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ketoprofen (C₁₆H₁₄O₃) in the portion of Capsules taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

The Standard solution and Sample solution must be protected from light.

Medium: 0.05 M phosphate buffer, pH 7.4; 1000 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: USP Ketoprofen RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary, to a concentration similar to that of the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 260 nm

Cell path length: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ketoprofen (C₁₆H₁₄O₃) dissolved:

Result = (A_U/A_S) × (C_S/L) × D × V × 100

A_U = absorbance from the Sample solution

A_S = absorbance from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Capsule)

D = dilution factor of the Sample solution

V = volume of Medium, 1000 mL

Tolerances: NLT 80% (Q) of the labeled amount of ketoprofen (C₁₆H₁₄O₃) is dissolved.

5 IMPURITIES

Organic Impurities

The System suitability solution, Standard solution, and Sample solution must be protected from light.

Buffer: 68.0 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.5 ± 0.05.

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

Diluent: Acetonitrile and water (2:3)

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

Standard solution: 2 μg/mL of USP Ketoprofen RS, 2 μg/mL of USP Ketoprofen Related Compound C RS, and 3 μg/mL of USP Ketoprofen

Related Compound D RS in Diluent

Sample solution: Nominally 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 volume: 20 μL

Run time: 7 times the retention time of ketoprofen

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 7.0 between ketoprofen related compound D and ketoprofen

Relative standard deviation: NMT 10% for the ketoprofen peak

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of the corresponding related compound from the Standard solution

C_S = concentration of the corresponding USP Ketoprofen Related Compound RS in the Standard solution (mg/mL); use the concentration of the USP Ketoprofen RS for unknown impurities

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

Acceptance criteria: See Table 1.

Table 1

^a 2-(3-Carboxyphenyl) propionic acid.

^b 3-Acetylbenzophenone.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Ketoprofen RS

(±)-m-Benzoylhydratropic acid.

C₁₆H₁₄O₃ 254.28

USP Ketoprofen Related Compound A RS

α-Methyl-3-(4-methylbenzoyl) benzeneacetic acid.

C₁₇H₁₆O₃ 268.31

USP Ketoprofen Related Compound C RS

2-(3-Carboxyphenyl) propionic acid.

C₁₀H₁₀O₄ 194.18

USP Ketoprofen Related Compound D RS

3-Acetylbenzophenone.

C₁₅H₂O₂ 224.25