Edition: BP 2025 (Ph. Eur. 11.6 update)
Diamorphine Tablets
General Notices
Action and use
Opioid receptor agonist analgesic.
DEFINITION
Diamorphine Tablets contain Diamorphine Hydrochloride.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of diamorphine hydrochloride, C21H23NO5,HCl,H2O
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 10 mg of Diamorphine Hydrochloride with 10 mL of dichloromethane, filter 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
Dissolution
Comply with the requirements in the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.1M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 15 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with water if necessary, to produce a solution expected to contain 0.0011% w/v of Diamorphine Hydrochloride.
(2) 0.0011% w/v of diamorphine hydrochloride BPCRS in the dissolution medium.
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 250 µL of each solution.
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 total content of C21H23NO5,HCl,H2O in the medium from the chromatograms obtained and using the declared content of C21H23NO5,HCl,H2O in diamorphine hydrochloride BPCRS.
LIMITS
The amount of diamorphine hydrochloride released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse a quantity powdered tablets containing 80 mg of Diamorphine Hydrochloride in 10 mL of water. (2) Dilute 1 volume of solution (1) to 100 volumes with water.
(3) Disperse a quantity of the powdered tablets to give a solution containing 0.1% w/v of Diamorphine Hydrochloride in 0.01M sodium hydroxide; the solution should be freshly prepared.
(4) Dilute 1 volume of solution (2) to 10 volumes with water.
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 50 µL of each solution.
(g) For solution (1), allow the chromatography to proceed for twice the retention time of the peak due to diamorphine.
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.
When the chromatograms are recorded under the prescribed conditions the retention time of diamorphine is about 20 minutes.
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 twice the area of the principal peak in the chromatogram obtained with solution (2) (2%); the area of any other secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (4) (0.2%); the sum of the areas of any other secondary peaks is not greater than half 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) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse a quantity of the powdered tablets containing 30 mg of Diamorphine Hydrochloride in water, dilute to 100 mL with water.
(2) 0.03% w/v of diamorphine hydrochloride BPCRS in water.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with an injection volume of 10 µL.
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 tablets using the declared content of C21H23NO5,HCl,H2Oin diamorphine hydrochloride BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph those listed under Diamorphine Hydrochloride.
