Betamethasone Valerate Ointment

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Betamethasone Valerate Ointment contains an amount of betamethasone valerate (C₂₇H₃₇FO₆) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of betamethasone (C₂₂H₂₉FO₅), in a suitable ointment base.

2 IDENTIFICATION

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

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

3 ASSAY

Procedure

Solution A: Water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent A: Tetrahydrofuran and water (50:50)

Diluent B: Acetonitrile and water (40:60)

System suitability solution: 25 µg/mL of USP Betamethasone Valerate RS and 10 µg/mL of USP Betamethasone Valerate Related Compound A RS in Diluent B. Sonicate to dissolve if necessary.

Standard solution: 25 µg/mL of USP Betamethasone Valerate RS in Diluent B. Sonicate to dissolve if necessary.

Sample solution: Nominally 20 µg/mL of betamethasone, prepared as follows. Transfer 1.0 mg of betamethasone from a portion of Ointment to a suitable glass centrifuge tube. Add 15.0 mL of Diluent A and mix with a vortex mixer to disperse the sample thoroughly. Add 35.0 mL of Diluent B and sonicate for 10 min with intermittent shaking. Centrifuge to obtain a clear supernatant and use the clear supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

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

Flow rate: 1 mL/min

Injection volume: 100 µL

Autosampler temperature: 4°

System suitability

Samples: System suitability solution and Standard solution

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

Suitability requirements

Resolution: NLT 2.0 between betamethasone valerate and betamethasone valerate related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of betamethasone (C₂₂H₂₉FO₅) in the portion of Ointment taken:

Result = (r₁/r₂) × (C₁/C₂) × (M₁/M₂) × 100

r₁ = peak response from the Sample solution

r₂ = peak response from the Standard solution

C₁ = concentration of USP Betamethasone Valerate RS in the Standard solution (µg/mL)

C₂ = nominal concentration of betamethasone in the Sample solution (µg/mL)

M₁ = molecular weight of betamethasone, 392.46

M₂ = molecular weight of betamethasone valerate, 476.58

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Organic Impurities

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

Standard solution: 0.25 µg/mL each of USP Betamethasone RS, USP Betamethasone Valerate RS, and USP Betamethasone Valerate Related Compound A RS in Diluent B. Sonicate to dissolve if necessary.

System suitability

Samples: System suitability solution and Standard solution

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

Suitability requirements

Resolution: NLT 2.0 between betamethasone valerate and betamethasone valerate related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each specified degradation product in the portion of Ointment taken:

Result = (r₁/r₂) × (C₁/C₂) × 100

r₁ = peak response of each specified degradation product from the Sample solution

r₂ = peak response of the corresponding USP Reference Standard from the Standard solution

C₁ = concentration of the corresponding USP Reference Standard in the Standard solution (µg/mL)

C₂ = nominal concentration of betamethasone in the Sample solution (µg/mL)

Calculate the percentage of each unspecified degradation product in the portion of Ointment taken:

Result = (r₁/r₂) × (C₁/C₂) × (M₁/M₂) × 100

r₁ = peak response of each unspecified degradation product from the Sample solution

r₂ = peak response of betamethasone valerate from the Standard solution

C₁ = concentration of USP Betamethasone Valerate RS in the Standard solution (µg/mL)

C₂ = nominal concentration of betamethasone in the Sample solution (µg/mL)

M₁ = molecular weight of betamethasone, 392.46

M₂ = molecular weight of betamethasone valerate, 476.58

Acceptance criteria: See Table 2. Disregard any impurity peak less than 0.1%.

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: Meets the requirements of the tests for absence of Staphylococcus aureus and Pseudomonas aeruginosa.

Minimum Fill 〈755〉: Meets the requirements

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in collapsible tubes or in tight containers, and avoid exposure to excessive heat.

USP Reference Standards 〈11〉

USP Betamethasone RS

USP Betamethasone Valerate RS

USP Betamethasone Valerate Related Compound A RS

9-Fluoro-11β,17-dihydroxy-16β-methyl-3,20-dioxopregna-1,4-dien-21-yl valerate.

C₂₇H₃₇FO₆ 476.58