Ribavirin Tablets

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 Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of ribavirin (C₈H₁₂N₄O₅).

2 IDENTIFICATION

A.

The retention time of the ribavirin peak from the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 4.0 g/L of sodium dihydrogen phosphate dihydrate in water. Adjust with 5% sodium hydroxide solution to a pH of 5.0 ± 0.05. Pass the solution through a suitable filter of 0.45-µm pore size.

Mobile phase: Acetonitrile and Buffer (1:49)

Diluent: Acetonitrile and water (3:7)

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

Standard solution: 0.03 mg/mL of USP Ribavirin RS in Mobile phase from the Standard stock solution

Sample stock solution:

Transfer a portion of ribavirin, equivalent to 1000 mg of ribavirin from finely powdered Tablets (NLT 10), to a 1000-mL volumetric flask.

Add about 750 mL of Diluent, and sonicate with occasional shaking for 30 min.

Cool to room temperature, dilute with Diluent to volume, and mix.

Centrifuge, and decant the supernatant.

Sample solution:

0.03 mg/mL of ribavirin in Mobile phase from the Sample stock solution.

Pass through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

Run time: 10 min

System suitability

Sample: Standard solution

Suitability requirements:

Column efficiency: NLT 2000 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

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

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of ribavirin from the Sample solution

rₛ = peak response of ribavirin from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer and Mobile phase: Proceed as directed in the Assay.

Standard solution: 0.22 mg/mL of USP Ribavirin RS in Medium

Sample solution: Pass the solution through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 10 µL

System suitability

Sample: Standard solution

Suitability requirements:

Column efficiency: NLT 2000 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Calculate the percentage of ribavirin (C₈H₁₂N₄O₅) dissolved:

Result = (rᵤ / rₛ) × (Cₛ / L) × V × 100

rᵤ = peak response of ribavirin from the Sample solution

rₛ = peak response of ribavirin from the Standard solution

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

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) dissolved.

Uniformity of Dosage Units 〈905〉

Meets the requirements.

5 IMPURITIES

Organic Impurities: Procedure 1

(If uracil and/or uridine are known impurities, Procedure 2 is recommended.)

Solution A: 3.4 g/L of potassium dihydrogen phosphate in water. Adjust with 5% potassium hydroxide to pH 5.00 ± 0.05. Pass through 0.45-µm filter.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Standard stock solution: 0.4 mg/mL of USP Ribavirin RS in Solution A

Standard solution: 1 µg/mL of USP Ribavirin RS in Solution A from the stock

Sample solution:

100 mg ribavirin from Tablets (NLT 20)

Sonicate 15 min in Solution A

Dilute to 200 mL

Filter 0.45-µm

Chromatographic system

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

Run time: 70 min (data collection first 55 min)

System suitability

Sample: Standard solution

Requirement: Relative standard deviation NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate % unknown impurity:

Result = (rᵢ / rₛ) × (Cₛ / Cᵤ) × 100

rᵢ = peak response of unknown impurity

rₛ = peak response of ribavirin in Standard

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

Cᵤ = nominal concentration in Sample (mg/mL)

Acceptance criteria: See Table 2

Disregard peaks <0.05%

ᵃ These are process impurities listed for information only.

ᵇ 1H-1,2,4-Triazole-3-carboxylic acid.

ᶜ 1-β-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxylic acid.

ᵈ 1H-1,2,4-Triazole-3-carboxamide.

ᵉ 1-β-D-Ribofuranosyl-1H-1,2,4-triazole-5-carboxamide.

ᶠ Methyl 1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxylate.

ᵍ 1-(5-O-Acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide.

ʰ 1-(5-O-Benzoyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide.

Organic Impurities: Procedure 2

(For known impurities uracil / uridine)

Buffer: 3.0 g/L dibasic potassium phosphate in water, adjusted to pH 6.0 ± 0.1 with phosphoric acid. Filter 0.45-µm.

Mobile phase: Methanol and Buffer (1:39)

Standard stock solution:

1 mg/mL each of USP Ribavirin RS, USP Ribavirin Related Compound A RS, USP Ribavirin Related Compound D RS, USP Uracil RS, USP Uridine RS

Standard solution: 0.01 mg/mL each standard from stock

Sensitivity solution: 0.5 µg/mL USP Ribavirin RS

Sample solution:

1.0 mg/mL ribavirin from Tablets (NLT 20)

Sonicate 15 min

Dilute to 1000 mL

Centrifuge 10 min

Chromatographic system

Mode: LC

Detector: UV 207 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection size: 10 µL

Run time: NLT 4.3 × ribavirin retention time

System suitability

Samples: Standard solution, Sensitivity solution

Requirements:

Signal-to-noise: NLT 10 (Sensitivity)

Relative standard deviation: NMT 2.0% (Standard)

Analysis

Samples: Standard solution and Sample solution

Calculate % impurity:

Result = (rᵢ / rₛ) × (Cₛ / Cᵤ) × 100

rᵢ = peak response of impurity

rₛ = peak response of corresponding reference standard (use ribavirin value for unknown)

Cₛ = concentration in Standard solution (mg/mL)

Cᵤ = nominal concentration in Sample (mg/mL)

Acceptance criteria: See Table 3

Disregard peaks <0.05%

ᵃ 1-β-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxylic acid.

ᵇ 1H-1,2,4-Triazole-3-carboxamide.

ᶜ Pyrimidine-2,4(1H,3H)-dione.

ᵈ 1-β-D-Ribofuranosylpyrimidine-2,4(1H,3H)-dione.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store 15°–30°.

Labeling: If Organic Impurities test other than Procedure 1 is used, labeling states which test the article complies with.

USP Reference Standards 〈11〉

USP Ribavirin RS

USP Ribavirin Related Compound A RS

C₈H₁₁N₃O₆ 245.19

USP Ribavirin Related Compound D RS

C₃H₄N₄O₂ 112.09

USP Uracil RS

C₄H₄N₂O₂ 112.09

USP Uridine RS

C₉H₁₂N₂O₆ 244.20