Betamethasone Dipropionate

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

C₂₈H₃₇FO₇                 504.59
Pregna-1,4-diene-3,20-dione, 9-uoro-11-hydroxy-16-methyl-17,21-bis(1-oxopropoxy)-, (11β,16β);
9-Fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate CAS RN: 5593-20-4; UNII: 826Y60901U.

1 DEFINITION

Betamethasone Dipropionate contains NLT 97.0% and NMT 103.0% of betamethasone dipropionate (C₂₈H₃₇FO₇), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M _{( CN 1-Mar-2020)}

B. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Sample solution: 1 mg/ml, in chloroform

Chromatographic system

Developing solvent system: Chloroform and acetone (7:1)

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Mobile phase: Acetonitrile and water (1 in 2) such that the retention times for betamethasone dipropionate and beclomethasone dipropionate are 14 and 18 min, respectively. Degas by sonicating for 5-10 min. Do not leave Mobile phase in the column overnight, but flush the system after use with water for 15 min, followed by methanol for 15 min.

Diluent: Acetic acid and methanol (1 in 1000)

Internal standard solution: 0.9 mg/mL of USP Beclomethasone Dipropionate RS in Diluent

Standard stock solution: 0.6 mg/mL of USP Betamethasone Dipropionate RS in Diluent

Standard solution: 0.3 mg/mL of USP Betamethasone Dipropionate RS and 0.45 mg/mL of USP Beclomethasone Dipropionate RS, prepared by combining 5.0 ml each of the Internal standard solution and the Standard stock solution

Sample stock solution: 0.6 mg/mL of Betamethasone Dipropionate in Diluent

Sample solution: 0.3 mg/mL of Betamethasone Dipropionate, prepared by combining 5.0 mL each of the Internal standard solution and the Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 or 240 nm

Column: 4-mm x 30-cm; packing L1

Injection volume: 5-25 µL

System suitability

Sample: Standard solution

Suitability requirements

Peak area ratios: The lowest and highest peak area ratios of three successive injections agree within 2.0%.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betamethasone dipropionate (C₂₈H₃₇FO₇) in the portion of Betamethasone Dipropionate taken:

Result = (R_u /R_s ) × (C_s /C_u ) × 100

R_u = peak height ratio of betamethasone dipropionate to the internal standard from the Sample solution

R_s = peak height ratio of betamethasone dipropionate to the internal standard from the Standard solution

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

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

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

4 IMPURITIES

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

ORGANIC IMPURITIES

Mobile phase: Acetonitrile and water (65:35)

System suitability solution: 0.05 mg/mL of USP Betamethasone Dipropionate RS and 0.05 mg/mL of USP Betamethasone Valerate RS in

Mobile phase

Sample solution: 0.3 mg/mL of Betamethasone Dipropionate in Mobile phase. Shake until dissolved.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 15-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 4.0 between betamethasone valerate and betamethasone dipropionate

Column efficiency: NLT 8000 theoretical plates

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Betamethasone Dipropionate taken:

Result = (r_u /r_T ) × 100

r_u = peak response for each impurity

r_T = sum of the responses for all the peaks

Acceptance criteria

Individual impurities: NMT 1.0%

Total impurities: NMT 2.0%

5 SPECIFIC TESTS

OPTICAL ROTATION, Specific Rotation(781S)

Sample solution: 10 mg/mL, in dioxane

Acceptance criteria: +63° to +70°

LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at 25°, excursions permitted between 15° and 30°.

USP REFERENCE STANDARDS (11)

USP Beclomethasone Dipropionate RS

USP Betamethasone Dipropionate RS

USP Betamethasone Valerate RS