Trifluridine

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

C₁₀H₁₁F₃N₂O₅ 296.20

Thymidine, α,α,α-trifluoro-;

2′-Deoxy-5-(trifluoromethyl)uridine CAS RN®: 70-00-8; UNII: RMW9V5RW38.

1 DEFINITION

Trifluridine contains NLT 98.0% and NMT 102.0% of trifluridine (C₁₀H₁₁F₃N₂O₅), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 25 µg/mL in 0.1 N hydrochloric acid

Acceptance criteria: Meets the requirements

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

3 ASSAY

Change to read:

3.1 Procedure

Mobile phase: 0.15% sodium citrate solution. Adjust with 1 N hydrochloric acid to a pH of 6.8.

Standard stock solution: 1 mg/mL of USP Trifluridine RS and 0.01 mg/mL each of USP Trifluridine Related Compound A RS and 5-(trifluoromethyl)uracil in water. [Note—This stock preparation may be stored at 0°–5° for 3 months.]

Standard solution: 0.2 mg/mL of USP Trifluridine RS and 0.002 mg/mL each of USP Trifluridine Related Compound A RS and 5-(trifluoromethyl)uracil in water from the Standard stock solution

Sample solution: 0.2 mg/mL of Trifluridine in water

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 25-cm; 10-µm packing L1
• Flow rate: 2 mL/min
• Injection volume: 10 µL
• Run time: NLT 3.75 times the retention time of trifluridine

System suitability

• Sample: Standard solution
• Suitability requirements
• Resolution: NLT 3.0 between 5-(trifluoromethyl)uracil and trifluridine related compound A; NLT 4.0 between trifluridine related compound A and trifluridine
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of trifluridine (C₁₀H₁₁F₃N₂O₅) in the portion of Trifluridine taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of trifluridine from the Sample solution

rₛ = peak response of trifluridine from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Change to read:

4.1 Organic Impurities

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of trifluridine related compound A and 5-(trifluoromethyl)uracil in the portion of Trifluridine taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of trifluridine related compound A or 5-(trifluoromethyl)uracil from the Sample solution

rₛ = peak response of trifluridine related compound A or 5-(trifluoromethyl)uracil from the Standard solution

Cₛ = concentration of USP Trifluridine Related Compound A RS or 5-(trifluoromethyl)uracil in the Standard solution (mg/mL)

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

Acceptance criteria: NMT 1.0% of each related compound

5 SPECIFIC TESTS

5.1 Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 30 mg/mL in water

Acceptance criteria: +47° to +51°

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Trifluridine RS

USP Trifluridine Related Compound A RS

5-Carboxy-2′-deoxyuridine.

C₁₀H₁₂N₂O₇ 272.22