Vinblastine Sulfate for Injection

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

1 DEFINITION

Change to read:

Vinblastine Sulfate for Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of vinblastine sulfate (C₄₆H₅₈N₄O₉ · H₂SO₄).

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

2 IDENTIFICATION

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

Sample: Use material previously dried in a vacuum at 60° for 16 h.

Acceptance criteria: Meets the requirements of 197K

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

2.3 C. Identification Tests-General 〈191〉, Chemical Identification Tests, Sulfate

Sample solution: 100 mg/mL in water

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 Procedure

Solution A: Diethylamine and water (14:986). Adjust with phosphoric acid to a pH of 7.5.

Solution B: Acetonitrile and methanol (20:80)

Mobile phase: Solution A and Solution B (38:62)

Standard solution: 0.4 mg/mL of USP Vinblastine Sulfate RS in water

System suitability solution: 0.4 mg/mL of USP Vincristine Sulfate RS in Standard solution. [Note-No loss on drying determination is needed for USP Vincristine Sulfate RS.]

Sample stock solution: Pipet a suitable volume of water into each of five containers of Vinblastine Sulfate for Injection to obtain a solution in each having a nominal concentration of 1 mg/mL of vinblastine sulfate. Insert the stopper, shake to mix, and combine the solutions from the five containers.

Sample solution: Nominally equivalent to 0.4 mg/mL of vinblastine sulfate in water, from the Sample stock solution

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 262 nm
• Columns
• Precolumn: Packed with porous silica gel; installed between the pump and the injector
• Analytical: 4.6-mm × 15-cm; 5-µm packing L1
• Flow rate: 2 mL/min
• Injection volume: 20 µL

System suitability

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of vinblastine sulfate (C₄₆H₅₈N₄O₉ · H₂SO₄) in the portion of Vinblastine Sulfate for Injection taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of vinblastine from the Sample solution

rₛ = peak response of vinblastine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

Change to read:

5.1 Organic Impurities

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

Sample solution A: Use the Sample solution, prepared as directed in the Assay.

Sample solution B: 16 µg/mL of vinblastine sulfate in water, from Sample solution A

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 262 nm
• Columns
• Precolumn: Packed with porous silica gel; installed between the pump and the injector
• Analytical: 4.6-mm × 15-cm; 5-µm packing L1
• Flow rate: 2 mL/min
• Injection volume: 200 µL (20 µL for System suitability)

Analysis

Samples: Sample solution A and Sample solution B

Calculate the percentage of each individual impurity in the portion of Vinblastine Sulfate for Injection taken:

Result = [r_UA/(Σr_UA+ 25r_UB)] × 100

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

r_UB = peak response of vinblastine from Sample solution B

Calculate the percentage of total impurities:

Result = [Σr_UA/(Σr_UA + 25r_UB)] × 100

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

r_UB = peak response of vinblastine from Sample solution B

Acceptance criteria

• Individual impurities: NMT 2.0%
• Total impurities: NMT 5.0%

6 SPECIFIC TESTS

Change to read:

Bacterial Endotoxins Test 〈85〉: Meets the requirements

Sterility Tests 〈71〉: Meets the requirements

Injections and Implanted Drug Products 〈1〉, Product Quality Tests Common to Parenteral Dosage Forms, Specific Tests, Completeness and Clarity of Solutions: At the time of use, it meets the requirements.

Other Requirements: It meets the requirements for Labeling 〈7〉, Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for Constitution, and store in a refrigerator.

Change to read:

Labeling: Label to indicate: “For Intravenous Use Only-Fatal If Given By Other Routes.” When dispensed, the container (holding the individual dose prepared for administration to the patient) must bear the statement: “For Intravenous Use Only-Fatal If Given By Other Routes.”

USP Reference Standards 〈11〉

USP Vinblastine Sulfate RS

USP Vincristine Sulfate RS

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