Betamethasone Valerate

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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1 DEFINITION

Betamethasone Valerate contains NLT 97.0% and NMT 103.0% of betamethasone valerate (C₂₇H₃₇FO₆), calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M or 197A (USP 1-Aug-2024)

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-Aug-2024)

3 ASSAY

Procedure

Mobile phase: Acetonitrile and water (50:50). [Note—The mobile phase composition should be tightly controlled (±2%) to maintain the elution order and resolution between specified and unspecified impurities.]

System suitability solution: 250 μg/mL of USP Betamethasone Valerate System Suitability Mixture RS and 2.5 µg/mL of USP Betamethasone Valerate Related Compound D RS in Mobile phase. Sonicate to dissolve.

Standard solution: 250 μg/mL of USP Betamethasone Valerate RS in Mobile phase. Sonicate to dissolve.

Sample solution: 250 μg/mL of Betamethasone Valerate in Mobile phase. Sonicate to dissolve.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of betamethasone valerate

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 5.0 between betamethasone valerate and betamethasone valerate related compound H;

NLT 1.5 between betamethasone valerate related compound H and betamethasone valerate related compound D, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.10%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betamethasone valerate (C₂₇H₃₇FO₆) in the portion of Betamethasone Valerate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of betamethasone valerate from the Sample solution

rₛ = peak response of betamethasone valerate from the Standard solution

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

Cᵤ = concentration of Betamethasone Valerate in the Sample solution (μg/mL)

(USP 1-Aug-2024)

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

4 IMPURITIES

Residue on Ignition 〈281〉

Analysis: Use a platinum crucible.

Acceptance criteria: NMT 0.2%

Limit of Betamethasone Valerate Related Compound H

Mobile phase: Acetonitrile and water (40:60)

Diluent: Acetonitrile and water (50:50)

System suitability solution: 250 µg/mL of USP Betamethasone Valerate System Suitability Mixture RS in Diluent. Sonicate to dissolve.

Standard solution: 0.375 µg/mL of USP Betamethasone Valerate RS in Diluent

Sample solution: 250 µg/mL of Betamethasone Valerate in Diluent. Sonicate to dissolve.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 1.4 mL/min

Injection volume: 75 µL

Run time: NLT 3 times the retention time of betamethasone valerate

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for betamethasone valerate and betamethasone valerate related compound H are 1.0 and 1.36, respectively.]

Suitability requirements

Resolution: NLT 7.5 between betamethasone valerate and betamethasone valerate related compound H, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betamethasone valerate related compound H in the portion of Betamethasone Valerate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of betamethasone valerate related compound H from the Sample solution

rₛ = peak response of betamethasone valerate from the Standard solution

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

Cᵤ = concentration of Betamethasone Valerate in the Sample solution (µg/mL)

F = relative response factor, 0.95

Acceptance criteria: NMT 0.15% (USP 1-Aug-2024)

Organic Impurities

[Note—Solutions containing betamethasone valerate should be prepared fresh and injected within 4 h.]

Mobile phase and System suitability solution: Prepare as directed in the Assay.

Sensitivity solution: 0.12 µg/mL of USP Betamethasone Valerate RS in Mobile phase

Standard solution: 1.75 µg/mL of USP Betamethasone RS, 0.25 µg/mL of USP Betamethasone Valerate RS, and 0.75 µg/mL of USP Betamethasone Valerate Related Compound A RS in Mobile phase

Sample solution: 250 µg/mL of Betamethasone Valerate in Mobile phase. Sonicate to dissolve.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 1.2 mL/min

Injection volume: 35 µL

Run time: NLT 2 times the retention time of betamethasone valerate

System suitability

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

Suitability requirements

Resolution: NLT 5.0 between betamethasone valerate and betamethasone valerate related compound H;

NLT 1.5 between betamethasone valerate related compound H and betamethasone valerate related compound D, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betamethasone and betamethasone valerate related compound A in the portion of Betamethasone Valerate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of betamethasone or betamethasone valerate related compound A from the Sample solution

rₛ = peak response of betamethasone or betamethasone valerate related compound A from the Standard solution

Cₛ = concentration of USP Betamethasone RS or USP Betamethasone Valerate Related Compound A RS in the Standard solution (μg/mL)

Cᵤ = concentration of Betamethasone Valerate in the Sample solution (μg/mL)

Calculate the percentage of 9-fluoroprednisolone 17-valerate, betamethasone valerate related compound C, betamethasone valerate related compound D, 6α-bromobetamethasone 17-valerate, and any unspecified impurity in the portion of Betamethasone Valerate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of 9-fluoroprednisolone 17-valerate, betamethasone valerate related compound C, betamethasone valerate related compound D, 6α-bromobetamethasone 17-valerate, or any unspecified impurity from the Sample solution

rₛ = peak response of betamethasone valerate from the Standard solution

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

Cᵤ = concentration of Betamethasone Valerate in the Sample solution (μg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

a. 9-Fluoro-11β,21-dihydroxy-3,20-dioxopregna-1,4-diene-17-yl valerate.

b. 9-Fluoro-11β,21-dihydroxy-16α-methyl-3,20-dioxopregna-1,4-dien-17-yl valerate; also known as Dexamethasone 17-valerate.

c. Also known as beclomethasone 17-valerate.

d. This impurity is quantified using the Limit of Betamethasone Valerate Related Compound H test.

e. Also known as 9α-bromobetamethasone 17-valerate.

f. Also known as betamethasone 21-valerate.

g. 6α-Bromo-9-fluoro-11β,21-dihydroxy-16β-methyl-3,20-dioxopregna-1,4-diene-17-yl valerate.

h. The sum of all impurities from the Organic Impurities and the Limit of Betamethasone Valerate Related Compound H tests.

(USP 1-Aug-2024)

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 10 mg/mL in dioxane

Acceptance criteria: +75° to +82°

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Betamethasone RS (USP 1-Aug-2024)

USP Betamethasone Valerate RS

USP Betamethasone Valerate Related Compound A RS

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

C₂₇H₃₇FO₆ 476.59

USP Betamethasone Valerate Related Compound D RS

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

C₂₇H₃₇BrO₆ 537.49

USP Betamethasone Valerate System Suitability Mixture RS

It contains a mixture of the following 2 compounds:

Betamethasone valerate

Betamethasone valerate related compound H: 9-Chloro-11β,21-dihydroxy-16β-methyl-3,20-dioxopregna-1,4-diene-17-yl valerate.

C₂₇H₃₇ClO₆ 493.04 (USP 1-Aug-2024)