Hydrocortisone Sodium Succinate

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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C₂₅H₃₃NaO₈ 484.51 

Pregn-4-ene-3,20-dione, 21-(3-carboxy-1-oxopropoxy)-11,17-dihydroxy-, monosodium salt, (11β)-; Cortisol 21-(sodium succinate) CAS RN®: 125-04-2; UNII: 50LQB69S1Z. 

1 DEFINITION 

Hydrocortisone Sodium Succinate contains NLT 97.0% and NMT 102.0% of total steroids, calculated as hydrocortisone sodium succinate (C₂₅H₃₃NaO₈), on the dried basis. 

2 IDENTIFICATION 

Infrared Absorption 

Sample: Transfer 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 those of a similar preparation of USP Hydrocortisone Hemisuccinate RS. 

Change to read: 

Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 20 µg/mL in methanol 

Analytical wavelength: 242 nm 

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%. 

Sodium compounds impart an intense yellow color to a nonluminous ame. 

3 ASSAY 

Assay for Steroids 〈351〉 

Blue tetrazolium solution: 5 mg/mL of blue tetrazolium in alcohol 

Tetramethylammonium hydroxide solution: Tetramethylammonium hydroxide TS in alcohol (1 in 10) 

Standard solution: 12.5 µg/mL of USP Hydrocortisone Hemisuccinate RS in alcohol 

Sample solution: 12.5 µg/mL of Hydrocortisone Sodium Succinate in alcohol 

Blank solution: Alcohol 

Analysis 

Samples: Standard solution, Sample solution, and Blank solution 

Transfer 20.0-mL aliquots of the Samples to separate glass-stoppered, 50-mL conical flasks. To each flask add 2.0 mL of Blue tetrazolium solution, mix, and add 4.0 mL of Tetramethylammonium hydroxide solution. Allow to stand in the dark for 90 min, and add 1.0 mL of glacial acetic acid. Concomitantly determine the absorbances of the solutions from the Sample solution and the Standard solution at about 525 nm, with a suitable spectrophotometer, against the blank. 

Calculate the percentage of total steroids, as hydrocortisone sodium succinate (C₂₅H₃₃NaO₈), in the portion of Hydrocortisone Sodium Succinate taken: 

Result = (A_U/A_S) × (C_S/C_U) × (M_r1/M_r2) × 100 

_AU = absorbance of the Sample solution

_AS = absorbance of the Standard solution

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

C_U = concentration of Hydrocortisone Sodium Succinate in the Sample solution (μg/mL)

M_r1 = molecular weight of hydrocortisone, 484.51

M_r2 = molecular weight of hydrocortisone hemisuccinate, 462.53

Acceptance criteria: 97.0%–102.0% on the dried basis 

4 SPECIFIC TESTS 

Sodium Content 

Sample: 1g 

Analysis: Dissolve the Sample, with gentle heating, in 75 mL of glacial acetic acid. Add 20 mL of dioxane, then add crystal violet TS, and titrate with 0.1 N perchloric acid VS. Each mL of 0.1 N perchloric acid is equivalent to 2.299 mg of sodium (Na). 

Acceptance criteria: 4.60%–4.84% on the dried basis 

Optical Rotation 〈781S〉, Procedures, Specific Rotation 

Sample solution: 10 mg/mL in alcohol 

Acceptance criteria: +140° to +150° 

Loss on Drying 〈731〉 

Analysis: Dry at 105° for 3 h. 

Acceptance criteria: NMT 2.0% 

5 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight, light-resistant containers. 

USP Reference Standards 〈11〉 

USP Hydrocortisone Hemisuccinate RS