Vinblastine Sulfate for Injection
DEFINITION
Vinblastine Sulfate for Injection is Vinblastine Sulfate suitable for parenteral use. It contains NLT 90.0% and NMT 110.0% of the labeled amount of vinblastine sulfate (C46H58N4O9·H2SO4).
[Caution—Handle Vinblastine Sulfate for Injection with great care because it is a potent cytotoxic agent. ]
IDENTIFICATION
•  A. Infrared Absorption 197K
Sample:  Use material previously dried in a vacuum at 60 for 16 h.
Acceptance criteria:  Meets the requirements
•  B. Identification Tests—General, Sulfate 191
Sample solution:  100 mg/mL in water
Acceptance criteria:  Meets the requirements
ASSAY
Change to read:
•  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 each of vincristine sulfate and vinblastine sulfate in water prepared as follows. Transfer USP Vincristine Sulfate RS or USP Vincristine Sulfate (Assay) RS(RB 1-Jul-2011) to a suitable volumetric flask, and dissolve in the Standard solution.
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 concentration of 1 mg/mL. Insert the stopper, shake to mix, and combine the solutions from the five containers.
Sample solution:  0.4 mg/mL of vinblastine sulfate in water from the Sample stock solution
Chromatographic system 
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; packing L1
Flow rate:  2 mL/min
Injection size:  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 vinblastine sulfate (C46H58N4O9·H2SO4) in the portion of Vinblastine Sulfate for Injection 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 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%
PERFORMANCE TESTS
•  Uniformity of Dosage Units 905
Procedure for content uniformity 
Buffer:  Dissolve 13.61 g of sodium acetate in 900 mL of water in a 1000-mL volumetric flask. Adjust with glacial acetic acid to a pH of 5.0 while stirring, and dilute with water to volume.
Standard solution:  40 µg/mL of USP Vinblastine Sulfate RS in Buffer
Sample solution:  Dissolve the contents of one container of Vinblastine Sulfate for Injection in Buffer to obtain a solution having a concentration of 40–50 µg/mL.
Instrumental conditions 
Mode:  UV
Analytical wavelength:  269 nm
Cell:  1 cm
Blank:  Buffer
Analysis 
Samples:  Standard solution and Sample solution
Concomitantly determine the absorbances of the Sample solution and the Standard solution, and calculate the percentage of vinblastine sulfate (C46H58N4O9·H2SO4) in the portion of Vinblastine Sulfate for Injection taken:
Result = (AU/AS) × (CS/CU) × 100
AU== absorbance of the Sample solution
AS== absorbance of 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:  Meets the requirements
IMPURITIES
•  Organic Impurities
Mobile phase, 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 from Sample solution A in water
Chromatographic system:  Proceed as directed in the Assay, except use an injection size of 200 µL.
Analysis 
Samples:  Sample solution A and Sample solution B
Calculate the percentage of each impurity in the portion of Vinblastine Sulfate for Injection taken:
Result = [rUA/(SrUA + 25rUB)] × 100
rUA== peak response of each impurity appearing after the solvent peak from Sample solution A
rUB== peak response of vinblastine from Sample solution B
Calculate the percentage of total impurities:
Result = [(SrUA/(SrUA + 25rUB)] × 100
rUA== peak response of each impurity appearing after the solvent peak from Sample solution A
rUB== peak response of vinblastine from Sample solution B
Acceptance criteria 
Individual impurities:  NMT 2.0%
Total impurities:  NMT 5.0%
SPECIFIC TESTS
•  Bacterial Endotoxins Test 85: It contains NMT 10.0 USP Endotoxin Units/mg of vinblastine sulfate.
•  Sterility Tests 71: Meets the requirements
•  Constituted Solution: At the time of use, it meets the requirements for Injections 1, Constituted Solutions.
•  Completeness of Solution 641: A 10-mg portion dissolves in 10 mL of Water for Injection to yield a clear solution.
•  Other Requirements: It meets the requirements for Injections 1, Labeling.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve as described in Injections 1, Containers for Sterile Solids, and store in a refrigerator.
•  Labeling: The label states: “Fatal if Given Intrathecally. For Intravenous Use Only.” When dispensed, the container or syringe (holding the individual dose prepared for administration to the patient) must be enclosed in an overwrap bearing the statement: “Do Not Remove Covering Until Moment of Injection. Fatal If Given Intrathecally. For Intravenous Use Only.”
Change to read:
•  USP Reference Standards 11
USP Endotoxin RS
USP Vinblastine Sulfate RS Click to View Structure
USP Vincristine Sulfate RS Click to View Structure
[Note—No loss on drying determination is needed for USP Vincristine Sulfate RS. ]
USP Vincristine Sulfate (Assay) RS
(RB 1-Jul-2011)
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USP35–NF30 Page 5021
Pharmacopeial Forum: Volume No. 37(3)