Betamethasone Sodium Phosphate

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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C₂₂H₂₈FNa₂O₈P                 516.40

Pregna-1,4-diene-3,20-dione, 9-uoro-11,17-dihydroxy-16-methyl-21-(phosphonooxy)-, disodium salt, (11β,16β)-; 9-Fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 21-(disodium phosphate) CAS RN: 151-73-5; UNII: 7BK02SCL3W

1 DEFINITION

Betamethasone Sodium Phosphate contains NLT 97.0% and NMT 103.0% of betamethasone sodium phosphate (C₂₂H₂₈FNa₂O₈P), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

B. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Standard solution: 1 mg/mL of USP Betamethasone Sodium Phosphate RS in methanol

Sample solution: 1 mg/mL of Betamethasone Sodium Phosphate in methanol

Chromatographic system

Application volume: 10 µL

Developing solvent system: 500 mL of butyl alcohol and 200 mL of dilute hydrochloric acid (1 in 12). Place in a separatory funnel, and mix.

Use the organic layer as the developing solvent.

Spray reagent: Sulfuric acid, methanol, and nitric acid (10:10:1)

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the chapter, except to spray the plate with Spray reagent, and heat at 105° for 10 min.

Acceptance criteria: Meets the requirements

C. IDENTIFICATION TESTS GENERAL, Sodium (191) and Phosphate (191)

Analysis: Ignite it at 800° (see Residue on Ignition (281)).

Acceptance criteria: The residue meets the requirements for sodium and phosphate.

3 ASSAY

PROCEDURE

Mobile phase: Methanol and 0.07 M anhydrous monobasic potassium phosphate (3:2)

Diluent: Methanol and water (3:2)

Standard solution: 0.17 mg/mL of USP Betamethasone Sodium Phosphate RS in Diluent

Sample solution: 0.17 mg/mL of Betamethasone Sodium Phosphate in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 30-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betamethasone sodium phosphate (C₂₂H₂₈FNa₂O₈P) in the portion of Betamethasone Sodium Phosphate 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 Betamethasone Sodium Phosphate RS in the Standard solution (mg/mL)

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

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

4 IMPURITIES

4.1 LIMIT OF PHOSPHATE IONS

Standard phosphate solution and Phosphate reagent A: Prepare as directed in Phosphate in Reagents (see Reagents, Indicators, and

Solutions-General Tests for Reagents).

Phosphate reagent B: Dissolve 350 mg of p-methylaminophenol sulfate in 50 mL of water. Add 20 g of sodium metabisulfite, mix to dissolve, and dilute with water to 100 mL

Standard solution: Dilute 5.0 mL of Standard phosphate solution in a mixture of 10 mL of water and 5 mL of 2 N sulfuric acid contained in a 25-mL volumetric flask, by warming if necessary. Add 1 mL each of Phosphate reagent A and Phosphate reagent B, dilute with water to 25.0 mL, mix, and allow to stand at room temperature for 30 min.

Sample solution: Dissolve 50 mg of Betamethasone Sodium Phosphate in a mixture of 10 mL of water and 5 mL of 2 N sulfuric acid contained in a 25-mL volumetric flask, by warming if necessary. Add 1 mL each of Phosphate reagent A and Phosphate reagent B, dilute with water to 25.0 mL, mix, and allow to stand at room temperature for 30 min.

Instrumental conditions

Mode: Vis

Analytical wavelength: Maximum absorbance at about 730 nm

Cell: 1 cm

Blank: Water

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The absorbance of the Sample solution is NMT that of the Standard solution. The limit is 1.0% of phosphate (PO₄).

4.2 LIMIT OF FREE BETAMETHASONE

Sample stock solution: 1.0 mg/mL of Betamethasone Sodium Phosphate in water, prepared as follows. Dissolve 25.0 mg of Betamethasone Sodium Phosphate in water to make 25.0 mL.

Sample solution: Transfer 5.0 mL of the Sample stock solution to a separator, and extract with three 25-ml portions of chloroform. Filter each extract through a chloroform-saturated cotton pledget, combining the filtrates in a conical flask. Evaporate the chloroform on a steam bath to dryness with the aid of a current of air, and dissolve the residue in methanol to make 25.0 mL.

Blank solution: Transfer 5.0 mL of water to a separator. Proceed as directed in Sample solution, beginning with "extract with three 25-mL portions of chloroform".

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 239 nm

Cell: 1 cm

Blank: Blank solution

Analysis

Sample: Sample solution

Calculate the quantity, in mg, of free betamethasone in the portion of Betamethasone Sodium Phosphate taken:

Result = A × 3.125

A = absorbance of the Sample solution

Acceptance criteria: NMT 0.25 mg (1.0%)

5 SPECIFIC TESTS

OPTICAL ROTATION, Specific Rotation(781S)

Sample solution: 10 mg/mL

Acceptance criteria: +99° to +105°

WATER DETERMINATION, Method (921): NMT 10.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Betamethasone Sodium Phosphate RS