Betamethasone Acetate

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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C₂₄H₃₁FO₆     434.50

Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17-dihydroxy-16-methyl-21-(acetyloxy)-, (113,168);

9-Fluoro-118,17,21-trihydroxy-16ẞ-methylpregna-1,4-diene-3,20-dione 21-acetate CAS RN: 987-24-6; UNII: T105A053L7.

1 DEFINITION

Betamethasone Acetate contains NLT 97.0% and NMT 103.0% of betamethasone acetate (C₂H₃, FO), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M or 197A _{(USP 1-Dec-2023)}

Change to read:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-Dec-2023)}

3 ASSAY

Change to read:

PROCEDURE

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Solution A and Solution B (44:56)

System suitability solution: 200 µg/mL of USP Betamethasone Acetate RS and 40 µg/mL each of USP Betamethasone Acetate Related Compound C RS, USP Betamethasone Acetate Related Compound D RS, and USP Dexamethasone Acetate RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution: 200 µg/mL of USP Betamethasone Acetate RS in Diluent. Sonicate to dissolve, if necessary.

Sample solution: 200 µg/mL of Betamethasone Acetate in Diluent. Sonicate to dissolve, if necessary.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 15-cm; 3.5-µm packing L1

Autosampler temperature: 4°

Flow rate: 0.8 mL/min

Injection volume: 15 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 3.0 between betamethasone acetate and dexamethasone acetate; NLT 1.2 between betamethasone acetate related

compound C and betamethasone acetate related compound D, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betamethasone acetate (C₂₄H₃₁FO₆) in the portion of Betamethasone Acetate taken:

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

r_u = peak response of betamethasone acetate from the Sample solution

r_s = peak response of betamethasone acetate from the Standard solution

C_s = concentration of USP Betamethasone Acetate RS in the Standard solution (µg/mL)

C_u = concentration of Betamethasone Acetate in the Sample solution (µg/mL)

Acceptance criteria: 97.0%–103.0% on the anhydrous basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.2%, a platinum crucible being used

Delete the following:

ORDINARY IMPURITIES (466) (USP 1-Dec-2023)

Add the following:

ORGANIC IMPURITIES

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

Standard solution: 0.2 µg/mL each of USP Betamethasone Acetate RS, USP Betamethasone RS, and USP Betamethasone Acetate Related Compound D RS, and 0.3 µg/mL each of USP Betamethasone Acetate Related Compound C RS and USP Dexamethasone Acetate RS in Diluent. Sonicate to dissolve, if necessary.

Sensitivity solution: 0.1 µg/ml of USP Betamethasone Acetate RS in Diluent. Sonicate to dissolve, if necessary.

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[NOTE-See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 3.0 between betamethasone acetate and dexamethasone acetate; NLT 1.2 between betamethasone acetate related compound C and betamethasone acetate related compound D, System suitability solution

Relative standard deviation: NMT 5.0% for all standard peaks, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of betamethasone, betamethasone related compound C, betamethasone related compound D, and dexamethasone acetate in the portion of Betamethasone Acetate taken:

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

r_u = peak response of betamethasone, betamethasone related compound C, betamethasone related compound D, or dexamethasone acetate from the Sample solution

r_s = peak response of betamethasone, betamethasone related compound C, betamethasone related compound D, or dexamethasone acetate from the Standard solution

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

C_u = concentration of Betamethasone Acetate in the Sample solution (µg/mL)

Calculate the percentage of isoupredone acetate, 11-desoxymeprednisone, and each unspecied impurity in the portion of

Betamethasone Acetate taken:

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

r_u = peak response of isoupredone acetate, 11-desoxymeprednisone, or any unspecied impurity from the Sample solution

r_s = peak response of betamethasone acetate from the Standard solution

C_s = concentration of USP Betamethasone Acetate RS in the Standard solution (µg/mL)

C_u = concentration of Betamethasone Acetate in the Sample solution (µg/mL)

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

Table 2

   ^a 9-Fluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate.

^b 17,21-Dihydroxy-16β-methylpregna-1,4-diene-3,20-dione.

5 SPECIFIC TESTS

OPTICAL ROTATION (781S), Procedures. Specific Rotation

Sample solution: 10 mg/mL of Betamethasone Acetate in dioxane

Acceptance criteria: +120° to +128°

WATER DETERMINATION (921), Method : NMT 4.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store between 2 and 30°.

Change to read:

USP REFERENCE STANDARDS (11)

USP Betamethasone RSA _{(USP 1-Dec-2023)}

USP Betamethasone Acetate RS

USP Betamethasone Acetate Related Compound CRS

9-Fluoro-118,17,21-trihydroxy-16ẞ-methylpregna-1,4-diene-3,20-dione 11,21-diacetate.

C₂₆H₃₃FO₇                476.53

USP Betamethasone Acetate Related Compound D RS

9,118-Epoxy-17,21-dihydroxy-16ẞ-methylpregna-1,4-diene-3,20-dione 21-acetate.

C₂₄H₃₀O₆                  414,49

USP Dexamethasone Acetate RS, _{(USP 1-Dec-2023)}