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4464 Ketoprofen / Official Monographs USP 39

IDENTIFICATION Analysis
• A. INFRARED ABSORPTION 〈197K〉 Samples: Standard solution and Sample solution
• B. ULTRAVIOLET ABSORPTION 〈197U〉 Calculate the percentage of each impurity in the por-
Analytical wavelength: 258 nm tion of Ketoprofen taken:
Medium: Methanol and water (3:1)
Blank: Medium Result = (rU/rS) × (CS/CU) × 100
Sample solution: 10 µg/mL in Medium
Acceptance criteria: Absorptivities, calculated on the rU = peak response of impurity from the Sample
dried basis, do not differ by more than 3.0%. solution
rS = peak response of ketoprofen from the
ASSAY Standard solution
• PROCEDURE CS = concentration of USP Ketoprofen RS in the
Sample: 450 mg Standard solution (mg/mL)
Titrimetric system CU = concentration of the Sample solution (mg/mL)
(See Titrimetry 〈541〉.) Acceptance criteria
Mode: Direct titration Any individual impurity: NMT 0.2%
Titrant: 0.1 N sodium hydroxide VS Total impurities: NMT 1.0%
Endpoint detection: Visual
Analysis: Dissolve the Sample in 25 mL of alcohol. Add SPECIFIC TESTS
25 mL of water and several drops of phenol red TS. • MELTING RANGE OR TEMPERATURE, Procedure for Class I
Perform a blank determination. Each mL of Titrant is 〈741〉: 92.0°–97.0°
equivalent to 25.43 mg of C16H14O3. [NOTE—Standard- • OPTICAL ROTATION, Specific Rotation 〈781S〉
ize the 0.1 N sodium hydroxide by a similar titration of Sample solution: 10 mg/mL, in dehydrated alcohol
primary standard benzoic acid.] Acceptance criteria: +1° to −1°
Acceptance criteria: 98.5%–101.0% on the dried basis • LOSS ON DRYING 〈731〉: Dry a sample in a vacuum at 60°
for 4 h: it loses NMT 0.5% of its weight.
IMPURITIES
• RESIDUE ON IGNITION 〈281〉: NMT 0.2% ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers.
• USP REFERENCE STANDARDS 〈11〉
Delete the following: USP Ketoprofen RS
USP Ketoprofen Related Compound D RS
•• HEAVY METALS, Method II 〈231〉: NMT 0.002%• (Official 1-
.

3-Acetylbenzophenone.
Jan-2018)
• 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 ±
.

Ketoprofen Capsules
USP Monographs

0.05
Mobile phase: Acetonitrile, water, and Buffer (43:55:2) DEFINITION
System suitability solution: 5 µg/mL of USP Ketoprofen Capsules contain NLT 90.0% and NMT 110.0%
Ketoprofen RS and 1.5 µg/mL of USP Ketoprofen Re- of the labeled amount of ketoprofen (C16H14O3).
lated Compound D RS in Mobile phase
Standard solution: 0.002 mg/mL of USP Ketoprofen RS IDENTIFICATION
in Mobile phase • A. INFRARED ABSORPTION 〈197K〉
Sample solution: 1 mg/mL of Ketoprofen in Mobile Sample solution: Shake a quantity of the contents of
phase the Capsules containing 50 mg of ketoprofen with 5 mL
Chromatographic system of chloroform for 5 min, filter, and evaporate to dryness
(See Chromatography 〈621〉, System Suitability.) using a rotary evaporator.
Mode: LC Acceptance criteria: Meet the requirements
Detector: UV 233 nm • B. The retention time of the major peak of the Sample
Column: 4.6-mm × 15-cm; 5-µm packing L1 solution corresponds to that of the Standard solution, as
Flow rate: 1 mL/min obtained in the Assay.
Injection size: 20 µL
Run time: Seven times the retention time for ASSAY
Ketoprofen • PROCEDURE
System suitability The Standard solution and Sample solution must be pro-
Samples: System suitability solution and Standard tected from light.
solution Mobile phase: Acetonitrile, glacial acetic acid, and
[NOTE—The relative retention times for ketoprofen and water (90:1:110)
ketoprofen related compound D (3-acetylbenzophe- System suitability stock solution: 0.25 mg/mL of USP
none) are about 1.0 and 1.6, respectively.] Ketoprofen RS and 0.5 mg/mL of USP Ketoprofen Re-
Suitability requirements lated Compound A RS in Mobile phase
Resolution: NLT 7.0 between ketoprofen related System suitability solution: 0.02 mg/mL of USP
compound D and ketoprofen, System suitability Ketoprofen RS and 0.04 mg/mL of USP Ketoprofen Re-
solution lated Compound A RS in Mobile phase from System suit-
Column efficiency: NLT 2250 theoretical plates from ability stock solution
ketoprofen, System suitability solution Standard stock solution: 0.24 mg/mL of USP
Tailing factor: NMT 2.0 for ketoprofen, System suita- Ketoprofen RS in Mobile phase
bility solution Standard solution: 0.024 mg/mL of USP Ketoprofen RS
Relative standard deviation: NMT 5%, Standard in Mobile phase from Standard stock solution
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 trans-
fer a quantity of the contents, equivalent to 200 mg of

Official from May 1, 2016

Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
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USP 39 Official Monographs / Ketoprofen 4465

ketoprofen, to a 250-mL volumetric flask. Add 150 mL IMPURITIES

of Mobile phase, stir for 2 h, then dilute with Mobile • ORGANIC IMPURITIES
phase to volume. Centrifuge a portion of the prepara- The System suitability solution, Standard solution, and
tion. Pipet 3.0 mL of clear supernatant into a 100-mL Sample solution must be protected from light.
volumetric flask. Dilute with Mobile phase to volume. Buffer: 68.0 g/L of monobasic potassium phosphate in
Chromatographic system water. Adjust with phosphoric acid to a pH of 3.5 ±
(See Chromatography 〈621〉, System Suitability.) 0.05.
Mode: LC Mobile phase: Acetonitrile, water, and Buffer (43:55:2)
Detector: UV 250 nm Diluent: Acetonitrile and water (2:3)
Column: 4.6-mm × 25-cm; 5-µm packing L1 System suitability solution: 5 µg/mL of USP
Flow rate: 1.2 mL/min Ketoprofen RS and 1.5 µg/mL of USP Ketoprofen Re-
Injection volume: 20 µL lated Compound D RS in Diluent
System suitability Standard solution: 2 µg/mL of USP Ketoprofen RS,
Samples: System suitability solution and Standard 2 µg/mL of USP Ketoprofen Related Compound C RS,
solution and 3 µg/mL of USP Ketoprofen Related Compound D
Suitability requirements RS in Diluent
Resolution: NLT 3.0 between ketoprofen and Sample solution: Nominally 1 mg/mL of ketoprofen in
ketoprofen related compound A, System suitability Mobile phase
solution Chromatographic system
Tailing factor: NMT 1.5 for the ketoprofen peak, (See Chromatography 〈621〉, System Suitability.)
System suitability solution Mode: LC
Relative standard deviation: NMT 2.0%, Standard Detector: UV 233 nm
solution Column: 4.6-mm × 15-cm; 5-µm packing L1
Analysis Flow rate: 1 mL/min
Samples: Standard solution and Sample solution Injection volume: 20 µL
Calculate the percentage of the labeled amount of Run time: 7 times the retention time of ketoprofen
ketoprofen (C16H14O3) in the portion of Capsules taken: System suitability
Sample: System suitability solution
Result = (rU/rS) × (CS/CU) × 100 Suitability requirements
Resolution: NLT 7.0 between ketoprofen related
rU = peak response from the Sample solution compound D and ketoprofen
rS = peak response from the Standard solution Relative standard deviation: NMT 10% for the
CS = concentration of USP Ketoprofen RS in the ketoprofen peak
Standard solution (mg/mL) Analysis
CU = nominal concentration of ketoprofen in the Samples: Standard solution and Sample solution
Sample solution (mg/mL) Calculate the percentage of each impurity in the por-
Acceptance criteria: 90.0%–110.0% tion of Capsules taken:

USP Monographs
PERFORMANCE TESTS Result = (rU/rS) × (CS/CU) × 100

Change to read: rU = peak response of each impurity from the

Sample solution
• DISSOLUTION 〈711〉 rS = peak response of the corresponding related
The Standard solution and Sample solution must be pro- compound from the Standard solution
tected from light. CS = concentration of the corresponding USP
Medium: 0.05 M phosphate buffer, pH 7.4; 1000 mL Ketoprofen Related Compound RS in the
Apparatus 2: 50 rpm Standard solution (mg/mL); use the
Time: 30 min concentration of the USP Ketoprofen RS for
Standard solution: USP Ketoprofen RS in Medium unknown impurities
Sample solution: Pass a portion of the solution under CU = nominal concentration of ketoprofen in the
test through a suitable filter. Dilute with Medium, if nec- Sample solution (mg/mL)
essary, to a concentration similar to that of the Stan- Acceptance criteria: See Table 1.
dard solution.
Instrumental conditions Table 1
(See •Ultraviolet-Visible Spectroscopy 〈857〉• (CN 1-May-2016).)
.

Relative Acceptance
Mode: UV Retention Criteria,
Analytical wavelength: 260 nm Name Time NMT (%)
Cell path length: 1 cm
Ketoprofen related compound Ca 0.3 0.2
Blank: Medium .

Analysis Ketoprofen 1.0 —

Samples: Standard solution and Sample solution Ketoprofen related compound Db . 1.5 0.3
Calculate the percentage of the labeled amount of Individual unspecified impurity — 0.2
ketoprofen (C16H14O3) dissolved: Total impurities — 0.5
a 2-(3-Carboxyphenyl) propionic acid.
Result = (AU/AS) × (CS/L) × D × V × 100
.

b 3-Acetylbenzophenone.
.

AU = absorbance from the Sample solution ADDITIONAL REQUIREMENTS

AS = absorbance from the Standard solution • PACKAGING AND STORAGE: Preserve in tight containers,
CS = concentration of the Standard solution and store at controlled room temperature.
(mg/mL) • USP REFERENCE STANDARDS 〈11〉
L = label claim (mg/Capsule) USP Ketoprofen RS
D = dilution factor of the Sample solution (±)-m-Benzoylhydratropic acid.
V = volume of Medium, 1000 mL C16H14O3 254.28
Tolerances: NLT 80% (Q) of the labeled amount of
ketoprofen (C16H14O3) is dissolved.

Official from May 1, 2016

Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.
 Accessed from 10.6.1.1 by merck1 on Fri Jun 03 06:24:57 EDT 2016

4466 Ketoprofen / Official Monographs USP 39

USP Ketoprofen Related Compound A RS Analysis

α-Methyl-3-(4-methylbenzoyl) benzeneacetic acid. Samples: Standard solution and Sample solution
C17H16O3 268.31 Calculate the percentage of C16H14O3 in the portion of
USP Ketoprofen Related Compound C RS Capsules taken:
2-(3-Carboxyphenyl) propionic acid.
C10H10O4 194.18 Result = (rU/rS) × (CS/CU) × 100
USP Ketoprofen Related Compound D RS
3-Acetylbenzophenone. rU = peak response from the Sample solution
C15H12O2 224.25 rS = peak response from the Standard solution
CS = concentration of USP Ketoprofen RS in the
Standard solution (mg/mL)
CU = concentration of ketoprofen in the Sample
solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
.

Ketoprofen Extended-Release Capsules

PERFORMANCE TESTS
DEFINITION • DISSOLUTION 〈711〉
Ketoprofen Extended-Release Capsules contain NLT 90.0% Medium: pH 6.8 phosphate buffer; 1000 mL
and NMT 110.0% of the labeled amount of ketoprofen Apparatus 2: 50 rpm
(C16H14O3). Time: 1, 4, and 8 h
Detector: UV 258 nm
IDENTIFICATION Standard solution: About 0.1 mg/mL of USP
• A. The retention time of the major peak of the Sample Ketoprofen RS in Medium
solution corresponds to that of the Standard solution, as Sample solution: Pass a portion of the solution under
obtained in the Assay. test through a suitable filter of 10-µm pore size, then
• B. ULTRAVIOLET ABSORPTION 〈197〉: The UV spectrum from pass the filtrate through a suitable filter of 0.45-µm
the Sample solution in the Analysis for the Dissolution sec- pore size.
tion corresponds to the spectrum from the Standard solu- Capsules labeled to contain 200 mg: In a test tube,
tion. dilute 5.0 mL of filtrate with 5.0 mL of Medium.
ASSAY Capsules labeled to contain 150 mg: In a test tube,
• PROCEDURE dilute 6.0 mL of filtrate with 3.0 mL of Medium.
[NOTE—Protect the Standard solution and Sample solution Capsules labeled to contain 100 mg: No dilution is
from light.] necessary.
Mobile phase: Acetonitrile, water, and glacial acetic Capsule blank: Place 10 empty, clean Capsules of the
acid (90:110:1) appropriate dosage into a 1000-mL volumetric flask.
Standard stock solution: 0.24 mg/mL of USP Add about 800 mL of Medium at 37°. Stir until Capsule
Ketoprofen RS in Mobile phase shells are disintegrated. After equilibration to room tem-
Standard solution: 0.024 mg/mL of USP Ketoprofen RS perature, dilute with Medium to volume. Transfer
USP Monographs

in Mobile phase, from the Standard stock solution 100.0 mL to a 1000-mL volumetric flask, and dilute
System suitability solution: 0.25 mg/mL of USP with Medium to volume. Pass through a suitable filter of
Ketoprofen RS and 0.5 mg/mL of USP Ketoprofen Re- 10-µm pore size, then pass the filtrate through a suita-
lated Compound A RS in Mobile phase. Pipet 4.0 mL of ble filter of 0.45-µm pore size.
this solution into a 50-mL volumetric flask, and dilute Capsules labeled to contain 200 mg: In a flask, dilute
with Mobile phase to volume. 25.0 mL with 25.0 mL of Medium.
Sample solution: Remove completely the contents of Capsules labeled to contain 150 mg: In a flask, dilute
NLT 20 Capsules, and transfer a quantity of the beads, 30.0 mL with 15.0 mL of Medium.
equal to 200 mg of ketoprofen, to a 250-mL volumetric Capsules labeled to contain 100 mg: No dilution is
flask. Add 150 mL of Mobile phase and mix; bring to necessary.
volume. Centrifuge, and pipet 3.0 mL of clear superna- Analysis
tant that contains about 2.4 mg of ketoprofen into a Samples: Standard solution, Sample solution, and Cap-
100-mL volumetric flask. Dilute with Mobile phase to sule blank, using Medium as the blank
volume. Calculate the concentration, in mg/mL, of ketoprofen in
Chromatographic system the sample withdrawn at each time point:
(See Chromatography 〈621〉, System Suitability.)
Mode: LC Result = (AU − ACB) × (CS/AS)
Detector: UV 254 nm AU = absorbance of the Sample solution
Column: 4.6-mm × 25-cm; 5-µm packing L1 ACB = absorbance of the Capsule blank
Flow rate: 1.2 mL/min CS = concentration of USP Ketoprofen RS in the
Injection size: 20 µL Standard solution (mg/mL)
System suitability AS = absorbance of the Standard solution
Samples: Standard solution and System suitability Calculate the percentage of ketoprofen dissolved at
solution each time point:
Suitability requirements
Resolution: NLT 3.0 between ketoprofen and Result = (D + ΣR) × 100/L
ketoprofen related compound A, System suitability
solution D = [amount dissolved (mg)] = volume (mL)
Tailing factor: NMT 1.5 for the ketoprofen peak, Sys- remaining before draw × concentration
tem suitability solution (mg/mL) of sample withdrawn at the
Relative standard deviation: NMT 2.0%, Standard sampling time point
solution R = [amount removed (mg)] = volume (mL) of
sample withdrawn × concentration (mg/mL)
of sample withdrawn at each time point
100 = conversion factor for percentage
L = Capsule label claim (mg)

Official from May 1, 2016

Copyright (c) 2016 The United States Pharmacopeial Convention. All rights reserved.