Oxycodone Hydrochloride Injection
Action and use
Opioid receptor agonist; analgesic.
DEFINITION
Oxycodone Injection is a sterile solution containing Oxycodone Hydrochloride.
The injection complies with the requirements under Parenteral Preparations and with the following requirements.
Content of oxycodone hydrochloride, C18H21NO4, HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Mix a quantity of the injection containing 50 mg of Oxycodone Hydrochloride with 10 mL of water, filter and make the filtrate alkaline with dilute ammonia R1. Allow the solution to stand until a precipitate is formed. Filter the solution and wash the precipitate with 10 mL of cold water. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of oxycodone hydrochloride (RS 457).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in 0.02M acetic acid.
(1) To a quantity of the injection containing 20 mg of Oxycodone Hydrochloride add sufficient 0.02M acetic acid toproduce 50 mL and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) Dilute 2 volume of solution (2) to 10 volumes.
(4) 0.0002% w/v of oxycodone impurity standard BPCRS.
(5) Dilute 1 volume of solution (3) to 4 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Kromasil C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 230 nm.
(f) Inject 100 μL of each solution.
MOBILE PHASE
Mobile phase A 70 volumes of acetonitrile, 100 volumes of methanol and 830 volumes of a 0.11% w/v solution of sodium heptanesulfonate monohydrate previously adjusted to pH 2.0 with 8M orthophosphoric acid. Mobile phase B 150 volumes of acetonitrile, 250 volumes of methanol and 600 volumes of a 0.11% w/v solution of sodium heptanesulfonate monohydrate previously adjusted to pH 2.0 with 8M orthophosphoric acid.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-60 | 100→50 | 0→50 | linear gradient |
| 60-62 | 50→100 | 50→0 | linear gradient |
| 62-70 | 100 | 0 | isocratic |
When the chromatograms are recorded using the prescribed conditions, the retention time of oxycodone is about 24 minutes. The retention times relative to oxycodone are: impurity D, about 1.18; impurity E, about 1.18 and impurity F, about 2.4.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to oxycodone and 14-hydroxycodeinone is at least 3.0.
LIMITS
Identify any peaks in the chromatogram obtained with solution (1) corresponding to thebaine and multiply the area of this peak by 0.5.
In the chromatogram obtained with solution (1):
the sum of the areas of any peaks corresponding to 14-hydroxycodeinone and hydrocodone is not greater than the area of
the principal peak in the chromatogram obtained with solution (2) (1%);
the area of any other secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);
the sum of the areas of any secondary peaks is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.05%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in 0.02M acetic acid.
(1) To a quantity of the injection containing 25 mg of Oxycodone Hydrochloride add sufficient 0.02M acetic acid to produce 50 mL and filter.Dilute 1 volume of the filtrate to 100 volumes with 0.02M acetic acid.
(2) 0.0005% w/v of oxycodone hydrochloride BPCRS.
(3) 0.0002% w/v of oxycodone impurity standard BPCRS in 0.02M acetic acid.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Kromasil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 230 nm.
(f) Inject 100 μL of each solution.
(g) For solution (3) allow the chromatography to proceed for 4 times the retention time of the peak due to oxycodone.
MOBILE PHASE
100 volumes of acetonitrile, 200 volumes of methanol and 700 volumes of a solution containing 0.11% w/v of sodium heptanesulfonate monohydrate previously adjusted to pH 2.0 with 8M orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to oxycodone and 14-hydroxycodeinone is at least 2.0.
DETERMINATION OF CONTENT
Calculate the total content of oxycodone hydrochloride, C18H21NO4, HCl, in the injection using the declared content of C18H21NO4, HCl in oxycodone hydrochloride BPCRS.
IMPURITIES
D. 7,8-didehydro-4,5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one (14-hydroxycodeinone);
E. 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one (hydrocodone);
F. 6,7,8,14-tetradehydro-4,5α-epoxy-3-6-dimethoxy-17-methylmorphinan (thebaine).
