Prednisone

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

Prednisone contains NLT 97.0% and NMT 102.0% of prednisone (C₂₁H₂₆O₅), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K▲ (CN 1-May-2020)

Analysis: If a difference appears, dissolve portions of both the sample and the Reference Standard in methanol, evaporate the solutions to dryness, and repeat the tests.

Acceptance criteria: Meets the requirements

B.

Analysis 1: Dissolve 6 mg in 2 mL of sulfuric acid, and allow to stand for 5 min.

Acceptance criteria 1: An orange color is produced.

Analysis 2: Pour the resulting solution from Analysis 1 into 10 mL of water.

Acceptance criteria 2: The color changes first to yellow and then, gradually, to bluish green.

3 ASSAY

Procedure

Mobile phase: Peroxide-free tetrahydrofuran, methanol, and water (250:62:688)

Diluent: Methanol and water (1:1)

Standard stock solution: 0.2 mg/mL of USP Prednisone RS in Diluent

Internal standard solution: 110 µg/mL of acetanilide in Diluent

Standard solution: 20 µg/mL of USP Prednisone RS and 11 µg/mL of acetanilide in Diluent from the Standard stock solution and the Internal standard solution, respectively. Prepare this solution fresh.

Sample stock solution: 0.2 mg/mL of Prednisone in Diluent

Sample solution: 20 µg/mL of Prednisone and 11 µg/mL of acetanilide in Diluent from the Sample stock solution and the Internal standard solution, respectively. Prepare this solution fresh.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm × 25-cm; packing L1

Flow rate: 1.0 mL/min

Injection volume: 10 µL

[Note—The retention times of acetanilide and prednisone are about 6 and 8 min, respectively.]

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 3 between prednisone and acetanilide

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of prednisone (C₂₁H₂₆O₅) in the portion of Prednisone taken:

Result = (Rᵤ / Rₛ) × (Cₛ / Cᵤ) × 100

Rᵤ = peak response ratio of prednisone to acetanilide from the Sample solution

Rₛ = peak response ratio of prednisone to acetanilide from the Standard solution

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

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

Acceptance criteria: 97.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉

Sample: 100 mg

Acceptance criteria: Negligible

Organic Impurities

Mobile phase: Chloroform and methanol (98:2)

Sample solution: 1.25 mg/mL of Prednisone in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 6.0-mm × 4.0-cm; packing L3

Flow rate: 1 mL/min

Injection volume: 5 µL

System suitability

Sample: Sample solution

Suitability requirements

Column efficiency: NLT 2500 theoretical plates

Relative standard deviation: NMT 2.0%

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Prednisone taken:

Result = (rᵢ / rₜ) × 100

rᵢ = peak response for each impurity

rₜ = sum of all the peak responses

Acceptance criteria

Any individual impurity: NMT 1.5%

Total impurities: NMT 2.0%

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation 〈781S〉

Sample solution: 5 mg/mL in dioxane

Acceptance criteria: +167° to +175°

Water Determination, Method I 〈921〉

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light and moisture. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Prednisone RS