Edition: BP 2025 (Ph. Eur. 11.6 update)
General Notices
Action and use
Adrenoceptor agonist; reversal of hypotension from spinal or epidural anaesthesia.
DEFINITION
Ephedrine Injection is a sterile solution of Ephedrine Hydrochloride. It is supplied as a ready-to-use solution in Water for Injections or it is prepared immediately before use in accordance with the manufacturer’s instructions from Ephedrine Sterile Concentrate.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
When supplied as a ready-to-use solution, the injection complies with the following requirements.
Content of ephedrine hydrochloride, C10H15NO,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a quantity of the injection containing 10 mg of Ephedrine Hydrochloride add 2 mL of 2M hydrochloric acid, shake with two 20-mL quantities of dichloromethane and discard the dichloromethane. Add 5M ammonia until the aqueous layer is alkaline, extract with two 30-mL quantities of a mixture of 3 volumes of dichloromethane and 1 volume of ethanol, dry the combined extracts over anhydrous sodium sulfate, filter and evaporate to dryness at a pressure of 2 kPa, heating gently to remove the last traces of solvent. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ephedrine hydrochloride (RS 436).
TESTS
Acidity or alkalinity
pH, 4.5 to 7.0, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a volume of the injection, if necessary, with sufficient of the mobile phase to produce a solution containing 0.75% w/v of Ephedrine Hydrochloride.
(2) Dilute 1 volume of solution (1) to 500 volumes with mobile phase.
(3) 0.01% w/v of ephedrine hydrochloride BPCRS and 0.01% w/v of pseudoephedrine hydrochloride BPCRS in mobile phase.
(4) Dilute 1 volume of solution (2) to 10 volumes with mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with phenyl silica gel for chromatography (5 µm) (Spherisorb Phenyl 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 257 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for three times the retention time of the peak due to ephedrine.
MOBILE PHASE
6 volumes of methanol and 94 volumes of a 1.16% w/v solution of ammonium acetate adjusted to pH 4.0 using glacial acetic acid.
When the chromatograms are recorded under the prescribed conditions, the retention time of ephedrine is about 13 minutes and the retention time of pseudoephedrine is about 16 minutes.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to ephedrine and pseudoephedrine is at least 2.0.
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) (0.2%);
the sum of the areas of any secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.02%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 50 mg of Ephedrine Hydrochloride with 30 mL of methanol for 10 minutes, add sufficient water to produce 50 mL, filter through glass-fibre paper (Whatman GF/C is suitable) and use the filtrate.
(2) 0.1% w/v of ephedrine hydrochloride BPCRS in methanol (60%).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 263 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
0.005M dioctyl sodium sulfosuccinate in a mixture of 1 volume of glacial acetic acid, 35 volumes of water and 65 volumes of methanol.
DETERMINATION OF CONTENT
Calculate the content of C10H15NO,HCl in the injection using the declared content of C10H15NO,HCl in ephedrine hydrochloride BPCRS.
EPHEDRINE STERILE CONCENTRATE
DEFINITION
Ephedrine Sterile Concentrate is a sterile solution of Ephedrine Hydrochloride in Water for Injections.
The concentrate complies with the requirements for Concentrates for Injections or Infusions stated under Parenteral Preparations and with the following requirements.
Content of ephedrine hydrochloride, C10H15NO,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a quantity of the concentrate containing 10 mg of Ephedrine Hydrochloride add 2 mL of 2M hydrochloric acid, shake with two 20-mL quantities of dichloromethane and discard the dichloromethane. Add 5M ammonia until the aqueous layer is alkaline, extract with two 30-mL quantities of a mixture of 3 volumes of dichloromethane and 1 volume of ethanol, dry the combined extracts over anhydrous sodium sulfate, filter and evaporate to dryness at a pressure of 2 kPa, heating gently to remove the last traces of solvent. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ephedrine hydrochloride (RS 436).
TESTS
Acidity
pH, 4.5 to 7.0, Appendix V L.
Related substances
Carry out the method described in the requirements for the ready to use injection.
ASSAY
Carry out the Assay described in the requirements for the ready to use injection.
