Hydrocortisone Butyrate

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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C₂₅H₃₆O₆ 432.55 

Pregn-4-ene-3,20-dione, 11,21-dihydroxy-17- (1-oxobutoxy)-, (11β)-; 

Cortisol 17-butyrate; 

11β,17,21-Trihydroxypregn-4-ene-3,20-dione 17-butyrate CAS RN®: 13609-67-1; UNII: 05RMF7YPWN. 

1 DEFINITION 

Hydrocortisone Butyrate contains NLT 97.0% and NMT 102.0% of hydrocortisone butyrate (C₂₅H₃₆O₆), calculated on the dried basis.

2 IDENTIFICATION 

Change to read: 

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

Change to read: 

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

Sample solution: 10 µg/mL in methanol 

Analytical wavelength: 242 nm 

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

3 ASSAY 

Procedure 

Mobile phase: Acetonitrile, glacial acetic acid, and water (76:1:124) 

Diluent A: Tetrahydrofuran and glacial acetic acid (1000:1) 

Diluent B: Methanol, water, and glacial acetic acid (500:500:1) 

System suitability stock solution: 0.1 mg/mL each of USP Hydrocortisone Butyrate RS and propyl 4-hydroxybenzoate in Diluent A System suitability solution: 0.02 mg/mL each of USP Hydrocortisone Butyrate RS and propyl 4-hydroxybenzoate in Diluent B, from System suitability stock solution 

Standard stock solution: 0.1 mg/mL of USP Hydrocortisone Butyrate RS in Diluent A 

Standard solution: 0.02 mg/mL of USP Hydrocortisone Butyrate RS in Diluent B, from Standard stock solution Sample stock solution: 0.1 mg/mL of Hydrocortisone Butyrate in Diluent A 

Sample solution: 0.02 mg/mL of Hydrocortisone Butyrate in Diluent B, from Sample stock solution 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.0-mm × 10-cm; packing L1 

Flow rate: 1 mL/min 

Injection volume: 5 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for propyl 4-hydroxybenzoate and hydrocortisone butyrate are 0.7 and 1.0, respectively.] Suitability requirements 

Resolution: NLT 4.0 between propyl 4-hydroxybenzoate and hydrocortisone butyrate, System suitability solution Column efficiency: NLT 4000 theoretical plates, Standard solution 

Tailing factor: NMT 1.6, Standard solution 

Relative standard deviation: NMT 2.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of hydrocortisone butyrate (C₂₅H₃₆O₆) in the portion of Hydrocortisone Butyrate taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response from the Sample solution  

r_S = peak response from the Standard solution 

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

C_U = nominal concentration of Hydrocortisone Butyrate in the Sample solution (µg/mL) 

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

4 IMPURITIES 

Organic Impurities 

Solution A: 1 g of monobasic potassium phosphate in 1000 mL of water, adjusted with 45% potassium hydroxide to a pH of 5.5 Solution B: Acetonitrile 

Mobile phase: See Table 1. 

Table 1 

Diluent: Acetonitrile and Solution A (80:20) 

Standard solution: 0.5 mg/mL of USP Hydrocortisone Butyrate RS in Diluent 

Sample solution: 1 mg/mL of Hydrocortisone Butyrate in Diluent 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 10-cm; 3-µm packing L1 

Flow rate: 2 mL/min 

Injection volume: 5 µL 

System suitability 

Samples: Standard solution and Sample solution 

Suitability requirements 

Resolution: NLT 1.0 between hydrocortisone butyrate and any impurity 

Column efficiency: NLT 10,000 theoretical plates 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each impurity in the portion of Hydrocortisone Butyrate taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of each impurity from the Sample solution

r_S = peak response of hydrocortisone butyrate from the Standard solution

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

C_U = nominal concentration of Hydrocortisone Butyrate in the Sample solution (µg/mL) 

Acceptance criteria 

Disregard any peak having a percentage of 0.05% or less. 

Any individual impurity: NMT 1.0% 

Total impurities: NMT 2.0% 

5 SPECIFIC TESTS 

Optical Rotation, Specific Rotation〈781S〉 

Sample solution: 10 mg/mL, in chloroform 

Acceptance criteria: +47° to +54° at 20° 

Loss on Drying 〈731〉 

Sample: Dry Hydrocortisone Butyrate under vacuum at 78° for 3 h. 

Acceptance criteria: NMT 1.0% 

Completeness of Solution 〈641〉 

Sample solution: 1 g in 10 mL of dichloromethane 

Acceptance criteria: The Sample solution is clear. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. 

USP Reference Standards 〈11〉 

USP Hydrocortisone Butyrate RS