Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Corticosteroid.
DEFINITION
Hydrocortisone Sodium Succinate Injection is a sterile solution of Hydrocortisone Sodium Succinate in Water for Injections.
It is prepared by dissolving Hydrocortisone Sodium Succinate for Injection in the requisite amount of Water for Injections immediately before use.
The injection complies with the requirements stated under Parenteral Preparations.
STORAGE
Hydrocortisone Sodium Succinate Injection deteriorates on storage and should be used immediately after preparation.
HYDROCORTISONE SODIUM SUCCINATE FOR INJECTION
DEFINITION
Hydrocortisone Sodium Succinate for Injection is a sterile material prepared from Hydrocortisone Hydrogen Succinate with the aid of a suitable alkali. It may contain 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 hydrocortisone, C₂₁H₃₀O₅
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of hydrocortisone sodium succinate (RS 180).
B. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in 1 volume of methanol and 9 volumes of dichloromethane:
0.1% w/v solution of the contents of the sealed container.
0.1% w/v of hydrocortisone hydrogen succinate BPCRS.
0.1% w/v each of hydrocortisone hydrogen succinate BPCRS and methylprednisolone hydrogen succinate EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel GF254.
(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, allow to dry in air and examine in daylight and under ultraviolet light (365 nm).
MOBILE PHASE
1 volume of anhydrous formic acid, 10 volumes of absolute ethanol and 150 volumes of dichloromethane.
SYSTEM SUITABILITY
The test is not valid unless, by each method of visualisation, the chromatogram obtained with solution (3) shows two spots which may not be completely separated.
CONFIRMATION
By each method of visualisation, the principal spot in the chromatogram obtained with solution (1) corresponds in position to that in the chromatogram obtained with solution (2).
TESTS
Acidity or alkalinity
pH of a solution containing the equivalent of 5% w/v of hydrocortisone, 6.5 to 8.0, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Dissolve a sufficient quantity of the contents of the sealed container in a mixture of equal volumes of acetonitrile and water to produce a solution containing the equivalent of 0.25% w/v of hydrocortisone.
Dilute 2 volumes of solution (1) to 100 volumes with a mixture of equal volumes of acetonitrile and water.
Dilute 1 volume of a 0.035% w/v solution of hydrocortisone BPCRS in acetonitrile to 2 volumes with water.
Dilute a solution containing 0.04% w/v each of hydrocortisone hydrogen succinate BPCRS and dexamethasone BPCRS in acetonitrile with an equal volume of water.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (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.
(g) For solution (1) allow the chromatography to proceed for twice the retention time of the principal peak.
MOBILE PHASE
330 volumes of acetonitrile, 600 volumes of water and 1 volume of orthophosphoric acid which is allowed to equilibrate and then diluted to 1000 volumes with water.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks corresponding to dexamethasone and hydrocortisone hydrogen succinate is at least 5.0.
LIMITS
In the chromatogram obtained with solution (1):
The area of any peak corresponding to hydrocortisone is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (7%);
The area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (2%).
Uniformity of content
The content of hydrocortisone in each of 10 individual containers as determined in the Assay is not less than 92.5% and not more than 107.5% of the content of hydrocortisone stated on the label, except that in one container the weight may be not less than 85.0% and not more than 115.0% of the stated content.
ASSAY
Dissolve the contents of a sealed container in sufficient water to produce a solution containing the equivalent of 0.001% w/v of hydrocortisone. Measure the absorbance of the resulting solution at the maximum at 248 nm, Appendix II B, and calculate the content of C₂₁H₃₀O₅ taking 449 as the value of A(1%, 1 cm) at the maximum at 248 nm. Repeat the procedure with a further nine sealed containers and calculate the average content of C₂₁H₃₀O₅ per container from the ten individual results thus obtained.
LABELLING
The label of the sealed container states the quantity of hydrocortisone sodium succinate contained in it in terms of the equivalent amount of hydrocortisone.
