Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Intravenous general anaesthetic.
DEFINITION
Ketamine Injection is a sterile solution of Ketamine Hydrochloride in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of ketamine, C13H16ClNO
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Dilute a volume of the injection with a mixture of 1 volume of 1M sodium hydroxide and 49 volumes of methanol to produce a solution containing the equivalent of 0.07% w/v of ketamine. The light absorption, Appendix II B, in the range 230 to 350 nm of this solution exhibits a maximum at 301 nm and shoulders at 274, 268 and 261 nm.
B. Dilute a volume of the injection with 0.1M hydrochloric acid to produce a solution containing the equivalent of 0.025% w/v of ketamine. The light absorption, Appendix II B, in the range 230 to 350 nm of this solution exhibits two maxima at 276 nm and at 269 nm and a shoulder at 260 nm.
TESTS
Acidity
pH, 3.5 to 5.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute the injection, if necessary, to produce a solution containing the equivalent of 0.1% w/v of ketamine.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) Dilute 1 volume of solution (2) to 2 volumes.
(4) Add 2 volumes of a 0.05% w/v solution of ketamine impurity A EPCRS in the mobile phase to 1 volume of solution (1) and dilute the resulting solution to 100 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4.0 mm) and a stainless steel pre-column (4 mm × 4.0 mm), both packed with octadecylsilyl silica gel for chromatography (5 μm) (Lichrosorb RP18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 215 nm.
(f) Inject 20 μL of each solution.
(g) For solutions (1), (2) and (3), continue the chromatography for 10 times the retention time of ketamine.
MOBILE PHASE
Dissolve 0.95 g of sodium hexanesulfonate in 1 litre of a mixture of 25 volumes of acetonitrile R1 and 75 volumes of water.
To the resulting solution add 4 mL of 6M acetic acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks due to ketamine and ketamine impurity A is at least 1.5 and the retention time for ketamine is about 3 to 4.5 minutes. If necessary, adjust the concentrations of water and acetonitrile in the mobile phase.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of not more than one such peak is greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.25%);
the sum of the areas of all secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).
Disregard any peak with an area less than 0.4 times the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).
ASSAY
Dilute a volume of the injection containing the equivalent of 20 mg of ketamine to 100 mL with 0.05M hydrochloric acid and mix. Measure the absorbance of the resulting solution at the maximum at 269 nm, Appendix II B. Measure the absorbance of a 0.023% w/v solution of ketamine hydrochloride BPCRS in 0.05M hydrochloric acid at the same wavelength. Calculate the content of C13H16ClNO, using the declared content of C13H16ClNO, in ketamine hydrochloride BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurity A, listed under Ketamine Hydrochloride.
STORAGE
Ketamine Injection should be protected from light and stored at a temperature not exceeding 30°.
LABELLING
The quantity of active ingredient is stated in terms of the equivalent amount of ketamine.
