Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.
DEFINITION
Ketoprofen Injection is a sterile solution containing Ketoprofen. It is supplied as a ready-to-use solution.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of ketoprofen, C16H14O3
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Extract a volume of the injection containing 0.1 g of Ketoprofen, with two 5-mL quantities of dichloromethane. Retain and combine the lower layers, filter and evaporate to dryness under nitrogen. Dry the residue at 60° for 60 minutes. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ketoprofen (RSV 053).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared immediately before use in mobile phase.
(1) Dilute a quantity of the injection with sufficient mobile phase to produce a solution containing 0.1% w/v of Ketoprofen.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.0005% w/v of ketoprofen impurity A EPCRS.
(4) 0.0005% w/v of ketoprofen impurity C EPCRS.
(5) 0.0005% w/v of ketoprofen BPCRS and 0.0001% w/v of ketoprofen impurity A EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) with a specific surface area of 350 m2/g and a pore size of 10 nm (Nucleosil 100 C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 233 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for 7 times the retention time of ketoprofen.
MOBILE PHASE
2 volumes of freshly prepared phosphate buffer solution pH 3.5, 43 volumes of acetonitrile and 55 volumes of water.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to ketoprofen (retention time about 8 minutes) are: impurity C, about 0.3; impurity E, about 0.7; impurity B, about 0.8; impurity D, about 1.5; impurity A, about 1.6; impurity F, about 2.2.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between the peaks due to ketoprofen and impurity A is at least 7.0.
LIMITS
Use the chromatogram obtained with solution (3) to identify the peak due to impurity A; use the chromatogram obtained with solution (4) to identify the peak due to impurity C.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.5%);
the area of any peak corresponding to impurity C is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.5%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the sum of the areas of all the secondary peaks excluding impurities A and C is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than 0.6 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in mobile phase.
(1) Dilute a quantity of the injection, if necessary, with sufficient mobile phase to produce a solution containing 0.001% w/v of Ketoprofen.
(2) 0.001% w/v of ketoprofen BPCRS.
(3) 0.0005% w/v of ketoprofen BPCRS and 0.0001% w/v of ketoprofen impurity A EPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to ketoprofen and impurity A is at least 7.0.
DETERMINATION OF CONTENT
Calculate the content of C16H14O3 in the injection using the declared content of C16H14O3 in ketoprofen BPCRS.
STORAGE
Ketoprofen Injection should be stored protected from light.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Ketoprofen.
