Hydrocortisone Sodium Succinate for Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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DEFINITION 

Hydrocortisone Sodium Succinate for Injection is a sterile mixture of Hydrocortisone Sodium Succinate and suitable buffers. It may be prepared from Hydrocortisone Sodium Succinate, or from Hydrocortisone Hemisuccinate with the aid of Sodium Hydroxide or Sodium Carbonate. It contains the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of hydrocortisone (C₂₁H₃₀O₅) in single compartment containers, or in the volume of solution designated on the label of containers that are constructed to hold, in separate compartments, the Hydrocortisone Sodium Succinate for Injection and a solvent. 

1 IDENTIFICATION 

Infrared Absorption 

Sample: Transfer a quantity of Hydrocortisone Sodium Succinate for Injection, equivalent to 100 mg of hydrocortisone sodium succinate, to a suitable container, and dissolve in 10 mL of water. In rapid succession, add 1 mL of 3 N hydrochloric acid, shake briefly, immediately decant the aqueous layer, and wash the precipitate with two additional 10-mL portions of water, each time removing the water by decanting. Remove as much of the water as possible, spread the precipitate in a suitable container, and dry under vacuum at 60° for 3 h. Acceptance criteria: The IR spectrum of a Mineral oil dispersion of the precipitate so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Hydrocortisone Hemisuccinate RS. 

2 ASSAY 

Procedure 

Mobile phase: Butyl chloride, water-saturated butyl chloride, tetrahydrofuran, methanol, and glacial acetic acid (95:95:14:7:6) Internal standard solution: 3 mg/mL of USP Fluorometholone RS in tetrahydrofuran 

Diluent: Glacial acetic acid in chloroform (3 in 100) 

Solution A: 0.30 mg/mL of USP Hydrocortisone RS in Diluent 

Standard solution: 0.65 mg/mL of USP Hydrocortisone Hemisuccinate RS, prepared as follows. Transfer 32.5 mg of USP Hydrocortisone Hemisuccinate RS to a 50-mL volumetric flask. Add by pipet 5.0 mL of Internal standard solution and 5.0 mL of Solution A. Dilute with Diluent to volume. 

Sample solution: Mix the constituted solutions prepared from the contents of 10 vials of Hydrocortisone Sodium Succinate for Injection. Transfer a volume, equivalent to 50 mg of hydrocortisone from the resulting constituted solution, to a suitable flask containing 10.0 mL of Internal standard solution, and dilute with Diluent to 100.0 mL. Shake thoroughly for 5 min, then allow the phases to separate, discarding the upper phase. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.9-mm × 30-cm; packing L3 

Flow rate: 1.0 mL/min 

Injection volume: 6 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Resolution: NLT 2.0 between hydrocortisone hemisuccinate and the internal standard 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

[Note—The order of elution of peaks is that from the internal standard, hydrocortisone hemisuccinate, and successive smaller peaks representing free hydrocortisone and hydrocortisone 17-hemisuccinate, the relative retention times of which are about 1.0, 1.5, 2.0, and 2.5, respectively.] 

Calculate the percentage of the labeled amount of hydrocortisone (C₂₁H₃₀O₅) in the portion of Hydrocortisone Sodium Succinate for Injection taken: 

Result = (R_U/R_S) × (C_S/C_U) × (M_r1/M_r2) × 100 

R_U = ratio of the summation of the peak areas of hydrocortisone hemisuccinate and hydrocortisone 17-hemisuccinate to the peak  area of the internal standard from the Sample solution 

R_S = ratio of the summation of the peak areas of hydrocortisone hemisuccinate and hydrocortisone 17-hemisuccinate to the peak area of the internal standard from the Standard solution 

C_S = concentration of USP Hydrocortisone Hemisuccinate RS in the Standard solution (mg/mL) 

C_U = nominal concentration of the Sample solution (mg/mL) 

M_r1 = molecular weight of hydrocortisone, 362.46 

M_r2 = molecular weight of hydrocortisone hemisuccinate, 462.53 

To this percentage add the percentage of free hydrocortisone found in the test for Free Hydrocortisone. Acceptance criteria: 90.0%–110.0% 

3 OTHER COMPONENTS

Free Hydrocortisone 

Analysis: Using the chromatograms obtained in the Assay, measure the areas of the peaks from the internal standard and free hydrocortisone. 

Calculate the percentage of free hydrocortisone (C₂₁H₃₀O₅) in the portion of Hydrocortisone Sodium Succinate for Injection taken: 

Result = (R_U/R_S ) × (C_S /C_U) × 100 

R_U = peak area ratio of the free hydrocortisone to the internal standard from the Sample solution 

R_S = peak area ratio of the free hydrocortisone to the internal standard from the Standard solution 

C_S = concentration of USP Hydrocortisone RS in the Standard solution (mg/mL) 

C_U = nominal concentration of the Sample solution (mg/mL) 

Acceptance criteria: NMT 6.7% of the labeled amount of hydrocortisone 

4 PERFORMANCE TESTS 

Uniformity of Dosage Units 〈905〉: Meets the requirements 

5 SPECIFIC TESTS 

pH 〈791〉 

Sample solution: A solution containing the equivalent of 50 mg/mL of hydrocortisone 

Acceptance criteria: 7.0–8.0 

Loss on Drying 〈731〉 

Sample: Dry at 105° for 3 h. 

Acceptance criteria: NMT 2.0% 

Bacterial Endotoxins Test 〈85〉: Contains NMT 1.25 USP Endotoxin Units/mg of hydrocortisone 

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections 

Constituted Solution: At the time of use, it meets the requirements in Injections and Implanted Drug Products 〈1〉, Specic Tests, Completeness and clarity of solutions. 

Sterility Tests 〈71〉: Meets the requirements 

Other Requirements: It meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution. Labeling: Label it to indicate that the constituted solution prepared from Hydrocortisone Sodium Succinate for Injection is suitable for use only if it is clear, and that the solution is to be discarded after 3 days. Label it to indicate that it was prepared by freeze-drying, having been lled into its container in the form of a true solution. 

USP Reference Standards 〈11〉 

USP Fluorometholone RS 

USP Hydrocortisone RS 

USP Hydrocortisone Hemisuccinate RS