Ribavirin

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

Ribavirin contains NLT 98.9% and NMT 101.5% of ribavirin (C₈H₁₂N₄O₅), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. Thin-Layer Chromatographic Identification Test 〈201〉

Sample solution: 10 mg/mL

Developing solvent system: Acetonitrile and 0.1 M ammonium chloride (9:2)

Spray reagent: Anisaldehyde, sulfuric acid, glacial acetic acid, and alcohol (5:5:1:90)

Analysis: Proceed as directed in the chapter. Allow the plate to air-dry for 15 min, spray with Spray reagent, heat the plate at 110° for 30 min, and locate the spots on the plate by examining the plate in daylight.

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Mobile phase: Adjust water with sulfuric acid to a pH of 2.5 ± 0.1. Pass through a suitable filter of 0.5-µm or finer pore size.

Standard solution: 0.025 mg/mL of USP Ribavirin RS in Mobile phase

Sample solution: 0.025 mg/mL of Ribavirin in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 7.8-mm × 10-cm; packing L17

Column temperature: 65 ± 0.5°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: 0.7–1.5

Relative standard deviation: NMT 0.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ribavirin (C₈H₁₂N₄O₅) in the portion of Ribavirin taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Ribavirin RS in the Standard solution (mg/mL)

Cᵤ = concentration of Ribavirin in the Sample solution (mg/mL)

Acceptance criteria: 98.9%–101.5% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉

NMT 0.25%

Organic Impurities

Mobile phase, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample stock solution: 0.5 mg/mL of Ribavirin in Mobile phase

Analysis

Sample: Sample stock solution

Calculate the percentage of each peak, other than the solvent peak and the ribavirin peak, in the portion of Ribavirin taken:

Result = (rᵢ / rₜ) × 100

rᵢ = response of the individual peak

rₜ = sum of the responses of all the peaks

Acceptance criteria:

Any individual impurity: NMT 0.25%

Total impurities: NMT 1.0%

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation 〈781S〉

Sample solution: 10 mg/mL

Acceptance criteria: −33.5° to −37.0° (t = 20°)

pH 〈791〉

Sample solution: 20 mg/mL

Analysis: Add 0.2 mL of a saturated potassium chloride solution to 50 mL of Sample solution.

Acceptance criteria: 4.0–6.5

Loss on Drying 〈731〉

Analysis: Dry a sample at 105° for 5 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Ribavirin RS