Edition: BP 2025 (Ph. Eur. 11.6 update)
Dexamethasone Sodium Phosphate Injection
General Notices
Action and use
Glucocorticoid.
DEFINITION
Dexamethasone Sodium Phosphate Injection is a sterile solution of Dexamethasone Sodium Phosphate in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of dexamethasone, C22H29FO5
95.0 to 105.0% of the stated amount.
CHARACTERISTICS
A clear, colourless solution.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in methanol. (1) Dilute, if necessary, a volume of the injection to contain the equivalent of 0.08% w/v of dexamethasone. (2) 0.1% w/v of dexamethasone sodium phosphate BPCRS.
(3) 0.1% w/v each of dexamethasone sodium phosphate BPCRS and prednisolone sodium phosphate BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254 (Merck plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, heat at 110° for 10 minutes, spray the hot plate with ethanolic sulfuric acid (20%) and heat at 120° for 10 minutes; cool and examine in daylight and under ultraviolet light (365 nm).
MOBILE PHASE
20 volumes of acetic acid, 20 volumes of water and 60 volumes of butan-1-ol.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two spots which may, however, not be completely separated.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) is similar in position, colour in daylight, fluorescence in ultraviolet light at 365 nm and size to that in the chromatogram obtained with solution (2).
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
TESTS
Alkalinity
pH, 7.0 to 8.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in mobile phase A.
(1) Dilute a volume of the injection to produce a solution containing the equivalent of 0.08% w/v of dexamethasone. (2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.01% w/v each of dexamethasone sodium phosphate BPCRS and betamethasone sodium phosphate BPCRS. (4) 0.1% w/v of dexamethasone sodium phosphate for peak identification EPCRS.
(5) Dilute 1 volume of solution (2) to 5 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography R (5 µm) (Kromasil C8 is suitable).
(b) Use gradient 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 254 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1), continue the chromatography for twice the retention time of the principal peak.
MOBILE PHASE
Mobile phase A 300 volumes of 0.09M ammonium acetate and 350 volumes of water, adjusted to pH 3.8 with acetic acid, then add 350 volumes of methanol.
Mobile phase B 300 volumes of 0.09M ammonium acetate, adjusted to pH 4.0 with acetic acid, and 700 volumes of methanol.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
|---|---|---|---|
| 0–3.5 | 90 | 10 | isocratic |
| 3.5–23.5 | 90→60 | 10→40 | linear gradient |
| 23.5–34.5 | 60→5 | 40→95 | linear gradient |
| 34.5–50 | 5 | 95 | isocratic |
| 50–55 | 5→90 | 95→10 | linear gradient |
| 55–65 | 90 | 10 | re-equilibration |
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to betamethasone sodium phosphate and dexamethasone sodium phosphate is at least 2.0.
LIMITS
Identify any peak corresponding to impurity A in the chromatogram obtained with solution (1) using the chromatogram obtained with solution (4) and multiply the area by a correction factor of 0.75.
In the chromatogram obtained with solution (1):
the areas of any peak corresponding to impurity A, impurity B, impurity C, impurity D, impurity E, impurity F or impurity G are not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5% of each);
the area of any other secondary peak is not greater than 0.4 times 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 6 times the area of the principal peak in the chromatogram obtained with solution (2) (3%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute a volume of the injection to produce a solution containing the equivalent of 0.0066% w/v of dexamethasone. (2) 0.009% w/v of dexamethasone sodium phosphate BPCRS.
(3) 0.002% w/v each of dexamethasone sodium phosphate BPCRS and betamethasone sodium phosphate BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography R (5 µm) (Hypersil ODS 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 254 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
To 1.360 g of potassium dihydrogen phosphate add 0.600 g of hexylamine, mix, allow to stand for 10 minutes, dissolve in 182.5 mL of water, add 67.5 mL of acetonitrile, mix and filter (0.45 µm).
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to betamethasone sodium phosphate and dexamethasone sodium phosphate is at least 2.2.
DETERMINATION OF CONTENT
Calculate the content of C22H29FO5 in the injection from the peak areas obtained and from the declared content of C22H28FNa2O8P in dexamethasone sodium phosphate BPCRS. 1 mg of C22H28FNa2O8P is equivalent to 0.760 mg of C22H29FO5.
STORAGE
Dexamethasone Sodium Phosphate Injection should be protected from light. It should not be allowed to freeze.
LABELLING
The content of active ingredient is stated as the equivalent amount of dexamethasone in a suitable dose-volume.
IMPURITIES
The impurities limited by the requirements of this monograph those listed under Dexamethasone Sodium Phosphate and:
