Dexamethasone

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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C₂₂H₂₉FO₅ 392.46

Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-;

9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione CAS RN®: 50-02-2; UNII: 7S5I7G3JQL

1 DEFINITION

Dexamethasone contains NLT 97.0% and NMT 102.0% of dexamethasone (C₂₂H₂₉FO₅), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Solution A: 3.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Acetonitrile and water (56:44)

System suitability solution: 0.3 mg/mL of USP Dexamethasone RS and 20 µg/mL of USP Betamethasone RS in Diluent. Sonicate to dissolve as needed.

Standard solution: 0.3 mg/mL of USP Dexamethasone RS in Diluent. Sonicate to dissolve as needed.

Sample solution: 0.3 mg/mL of Dexamethasone in Diluent. Sonicate to dissolve as needed.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 240 nm
• Column: 2.1-mm × 10-cm; 1.7-µm packing L1
• Column temperature: 35°
• Flow rate: 0.4 mL/min
• Injection volume: 2 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-See Table 2 for the relative retention times.]
• Suitability requirements
• Resolution: NLT 1.5 between betamethasone and dexamethasone, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of dexamethasone (C₂₂H₂₉FO₅) in the portion of Dexamethasone 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 Dexamethasone RS in the Standard solution (mg/mL)

C_u = concentration of Dexamethasone in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Residue on Ignition 〈281〉

Sample: 250 mg

Analysis: Use a platinum crucible.

Acceptance criteria: NMT 0.2%

4.2 Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 4.0 µg/mL of USP Dexamethasone RS, 6.0 µg/mL each of USP Betamethasone RS and USP Desoximetasone RS, and 12.0 µg/mL of USP Dexamethasone Acetate RS in Diluent

Sample solution: 4.0 mg/mL of Dexamethasone in Diluent. Sonicate to dissolve as needed.

System suitability

• Samples: System suitability solution and Standard solution
• [NOTE-See Table 2 for the relative retention times.]
• Suitability requirements
• Resolution: NLT 1.5 between betamethasone and dexamethasone, System suitability solution
• Relative standard deviation: NMT 5.0% for betamethasone, dexamethasone, desoximetasone, and dexamethasone acetate, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betamethasone, desoximetasone, and dexamethasone acetate in the portion of Dexamethasone taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of betamethasone, desoximetasone, or dexamethasone acetate from the Sample solution 

r_s = peak response of the corresponding USP Reference Standard from the Standard solution 

C_s = concentration of the corresponding USP Reference Standard in the Standard solution (mg/mL)

C_u = concentration of Dexamethasone in the Sample solution (mg/mL)

Calculate the percentage of 16α-methylprednisone, dexamethasone 7,9-diene, and any individual unspecified impurity in the portion of Dexamethasone taken:

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100

r_u = peak response of 16a-methylprednisone, dexamethasone 7,9-diene, or any individual unspecified impurity from the Sample solution

r_s = peak response of dexamethasone from the Standard solution

C_s = concentration of USP Dexamethasone RS in the Standard solution (mg/mL)

C_u = concentration of Dexamethasone in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

ᵃ 17,21-Dihydroxy-16α-methylpregna-1,4-diene-3,11,20-trione.

ᵇ 17,21-Dihydroxy-16α-methylpregna-1,4,7,9(11)-tetraene-3,20-dione.

5 SPECIFIC TESTS

5.1 Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 10 mg/mL of Dexamethasone in dioxane

Acceptance criteria: +72° to +80°

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Betamethasone RS

USP Desoximetasone RS

USP Dexamethasone RS

USP Dexamethasone Acetate RS