Vincristine Sulfate

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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C₄₆H₅₆N₄O₁₀ · H₂SO₄ 923.04

Vincaleukoblastine, 22-oxo-, sulfate (1:1) (salt);

Leurocristine sulfate (1:1) (salt) CAS RN®: 2068-78-2; UNII: T5IRO3534A.

1 DEFINITION

Vincristine Sulfate contains NLT 95.0% and NMT 105.0% of vincristine sulfate (C₄₆H₅₆N₄O₁₀ · H₂SO₄), calculated on the dried basis.

[Caution-Handle vincristine sulfate with great care because it is a potent cytotoxic agent.]

2 IDENTIFICATION

Change to read:

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

2.2 B. Identification Tests-General 〈191〉, Chemical Identification Tests, Sulfate

Sample solution: 100 mg/mL

Acceptance criteria: Meets the requirements

2.3 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

Solution A: Diethylamine and water (1:59). Adjust with phosphoric acid to a pH of 7.5.

Mobile phase: Methanol and Solution A (70:30)

Standard solution: 1.2 mg/mL of USP Vincristine Sulfate RS in water

System suitability solution: 1 mg/mL of USP Vinblastine Sulfate RS in the Standard solution. [Note-No loss on drying determination is needed for USP Vinblastine Sulfate RS.]

Sample solution: 1.2 mg/mL of Vincristine Sulfate in water. Equilibrate a portion of Vincristine Sulfate for 30 min in ambient humidity. Using another portion of the equilibrated specimen, determine the loss on drying.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 297 nm
• Columns
• Precolumn: Porous silica gel packing
• Guard: 2- to 5-cm; packing L1
• Analytical: 4.6-mm × 25-cm; 5-µm packing L7
• Flow rate: 1.5 mL/min
• Injection volume: 10 µL

System suitability

• Samples: Standard solution and System suitability solution
• Suitability requirements
• Resolution: NLT 4.0 between the vincristine sulfate and vinblastine sulfate peaks, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of vincristine sulfate (C₄₆H₅₆N₄O₁₀ · H₂SO₄) in the portion of Vincristine Sulfate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of vincristine sulfate from the Sample solution

rₛ = peak response of vincristine sulfate from the Standard solution

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

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

Acceptance criteria: 95.0%–105.0% on the dried basis

4 IMPURITIES

4.1 Organic Impurities

Solution A: Diethylamine and water (3:197). Adjust with phosphoric acid to a pH of 7.5.

Solution B: Methanol

Mobile phase: See Table 1.

Table 1

Sample solution A: Prepare as directed for the Sample solution in the Assay.

Sample solution B: 0.04 mg/mL of Vincristine Sulfate in water, from Sample solution A

Chromatographic system: Proceed as directed in the Assay, except for the Flow rate and Injection volume.

• Flow rate: 2 mL/min
• Injection volume: 200 µL

Analysis

Samples: Sample solution A and Sample solution B

Calculate the percentage of each impurity in the portion of Vincristine Sulfate taken:

Result = [r_UA/(Σr_UA + 30r_UB)] × 100

r_UA = peak response of each impurity appearing after the solvent peak from Sample solution A

r_UB = peak response of vincristine from Sample solution B

Calculate the percentage of total impurities in the portion of Vincristine Sulfate taken:

Result = [Σr_UA/(Σr_UA + 30r_UB)] × 100

r_UA = peak response of each impurity appearing after the solvent peak from Sample solution A

r_UB = peak response of vincristine from Sample solution B

Acceptance criteria

• Individual impurities: NMT 1.0%
• Total impurities: NMT 4.0%

5 SPECIFIC TESTS

5.1 pH 〈791〉

Sample solution: 1 mg/mL

Acceptance criteria: 3.5–4.5

5.2 Loss on Drying

(See Thermal Analysis 〈891〉.)

[Note-In this procedure, perform weighings rapidly with minimum exposure of the substances to air.]

Sample: 10 mg

Analysis: Determine the percentage of volatile substances by thermogravimetric analysis on an appropriately calibrated instrument. Heat the Sample at the rate of 5°/min between ambient temperature and 200° in an atmosphere of nitrogen at a flow rate of 40 mL/min. From the thermogram, determine the accumulated loss in weight between ambient temperature and a point on the plateau before decomposition is indicated (at about 160°).

Acceptance criteria: NMT 12.0%

6 ADDITIONAL REQUIREMENTS

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

Change to read:

USP Reference Standards 〈11〉

USP Vinblastine Sulfate RS

[Note-No loss on drying determination is needed for USP Vinblastine Sulfate RS.]

USP Vincristine Sulfate RS