Edition: BP 2025 (Ph. Eur. 11.6 update)
Diamorphine Injection
General Notices
Action and use
Opioid receptor agonist analgesic.
DEFINITION
Diamorphine Injection is a sterile solution of Diamorphine Hydrochloride in Water for Injections. It is prepared by dissolving Diamorphine Hydrochloride for Injection in the requisite amount of Water for Injections immediately before use.
The injection complies with the requirements stated under Parenteral Preparations.
STORAGE
Diamorphine Injection deteriorates on storage and should be used immediately after preparation.
DIAMORPHINE HYDROCHLORIDE FOR INJECTION
DEFINITION
Diamorphine Hydrochloride for Injection is a sterile material prepared from Diamorphine Hydrochloride with or without excipients. It is supplied in a sealed container.
The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations and with the following requirements.
Content of diamorphine hydrochloride, C21H23NO5,HCl,H2O
92.5 to 105.0% of the stated amount.
IDENTIFICATION
Dissolve a sufficient quantity of the contents of the sealed container in the minimum volume of dichloromethane and evaporate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of diamorphine hydrochloride (RS 093).
TESTS
6-O-Acetylmorphine
Carry out the method for liquid chromatography, Appendix III D, using the following solutions freshly prepared.
(1) Dissolve a quantity of the powder for injection containing 0.2 g of Diamorphine Hydrochloride in 10 mL of water. (2) Dilute 1 volume of solution (1) to 20 volumes with water.
(3) Dilute 1 volume of solution (1) to 20 volumes with 0.01M sodium hydroxide.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (Lichrospher RP-select B 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 283 nm.
(f) Inject 20 µL of each solution.
When the chromatograms are recorded under the prescribed conditions, the retention time of diamorphine hydrochloride is about 20.3 minutes.
MOBILE PHASE
0.11% w/v of sodium octanesulfonate in a mixture of 10 volumes of glacial acetic acid, 10 volumes of methanol, 115 volumes of acetonitrile and 365 volumes of water.
SYSTEM SUITABILITY
The chromatogram obtained with solution (3) exhibits two secondary peaks with retention times relative to the principal peak of about 0.23 (morphine) and 0.43 (6-O-acetyl-morphine). The test is not valid unless the resolution between the peaks due to morphine and 6-O-acetyl-morphine is at least 2.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to 6-O-acetylmorphine is not greater than the area of the peak in the chromatogram obtained with solution (2) (5%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in water.
(1) Dissolve a quantity of the powder for injection containing 30 mg of Diamorphine Hydrochloride in 100 mL of water and filter.
(2) 0.03% w/v of diamorphine hydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS2 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 30°.
(e) Use a detection wavelength of 260 nm.
(f) Inject 10 µL of each solution.
When the chromatograms are recorded under the prescribed conditions, the retention time of diamorphine hydrochloride is about 3.5 minutes.
MOBILE PHASE
45 volumes of acetonitrile and 55 volumes of 0.01M sodium heptanesulfonate, containing 0.0075M N,N dimethyloctylamine, which has been adjusted to pH 3.0 with orthophosphoric acid.
DETERMINATION OF CONTENT
Calculate the content of C21H23NO5,HCl,H2O in the injection using the declared content of C21H23NO5,HCl,H2O in diamorphine hydrochloride BPCRS.
STORAGE
The sealed container should be protected from light.
IMPURITIES
The impurity limited by the requirements of this monograph is:
