Vinblastine Sulfate
C46H58N4O9·H2SO4 909.07
Vincaleukoblastine, sulfate (1:1) (salt);
Vincaleukoblastine sulfate (1:1) (salt)
[143-67-9].
11
USP Vincristine Sulfate (Assay) RS
(RB 1-Jul-2011)
(vin blas' teen sul' fate).
+'&img=../../images/v35300/cas-143-67-9.gif&casNumber=143-67-9&usp=35&nf=30&chemicalStructureImage=true&ID='+parent.myID,600,500);)
C46H58N4O9·H2SO4 909.07
Vincaleukoblastine, sulfate (1:1) (salt);
Vincaleukoblastine sulfate (1:1) (salt)
[143-67-9].DEFINITION
Vinblastine Sulfate contains NLT 96.0% and NMT 102.0% of C46H58N4O9·H2SO4, corrections being applied for loss in weight.
[Caution—Handle Vinblastine Sulfate with great care, because it is a potent cytotoxic agent.
]
IDENTIFICATION
• A. Infrared Absorption 197K
197K
Analysis:
The sample specimen and reference standard are previously dried in vacuum at 60
for 16 h.
for 16 h.
Acceptance criteria:
Meets the requirements
• B. Identification Tests—General, Sulfate 191
191
Sample:
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.
or USP Vincristine Sulfate (Assay) RS(RB 1-Jul-2011) to a suitable volumetric flask, and dissolve in the Standard solution.
Sample solution:
0.4 mg/mL of Vinblastine Sulfate in water
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 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 | = | = concentration of Vinblastine Sulfate in the Sample solution (mg/mL) |
Acceptance criteria:
96.0%–102.0%, corrections being applied for loss in weight
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 in the Assay.
Sample solution B:
16 µg/mL of vinblastine sulfate in water from Sample solution A
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:
200 µL
Analysis
Samples:
Sample solution A and Sample solution B
Calculate the percentage of each individual impurity in the portion of Vinblastine Sulfate taken:
Result = [rUA/(SrUA + 25rUB)] × 100
| rUA | = | = peak response for each individual impurity appearing after the solvent peak from Sample solution A |
| rUB | = | = peak response for vinblastine from Sample solution B |
Calculate the percentage of total impurities:
Result = [(SrUA/(SrUA + 25rUB)] × 100
| rUA | = | = peak response for each impurity appearing after the solvent peak from Sample solution A |
| rUB | = | = peak response for vinblastine from Sample solution B |
Acceptance criteria
Individual impurities:
NMT 1.0%
Total impurities:
NMT 3.0%
SPECIFIC TESTS
• Loss on Drying
(See Thermal Analysis 891.)
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 (about 160).
/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 (about 160).
Acceptance criteria:
It loses NMT 15.0% of its weight.
• Sterility Tests 71:
Where the label states that Vinblastine Sulfate is sterile, it meets the requirements.
71:
Where the label states that Vinblastine Sulfate is sterile, it meets the requirements.
• Bacterial Endotoxins Test 85:
Where the label states that Vinblastine Sulfate is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 10.0 USP Endotoxin Units/mg of vinblastine sulfate.
85:
Where the label states that Vinblastine Sulfate is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 10.0 USP Endotoxin Units/mg of vinblastine sulfate.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store in a freezer.
• Labeling:
Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
Change to read:
• USP Reference Standards 11
USP Endotoxin RS
USP Vinblastine Sulfate RS 
') + '&img=../../images/v35300/cas-143-67-9.gif',600,500);)
USP Vincristine Sulfate RS
[Note—No loss on drying determination is needed. ]
') + '&img=../../images/v35300/cas-2068-78-2.gif',600,500);)
USP Vincristine Sulfate (Assay) RS
(RB 1-Jul-2011)
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Feiwen Mao, M.S.
Senior Scientific Liaison 1-301-816-8320 |
(SM32010) Monographs - Small Molecules 3 |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 5020
Pharmacopeial Forum: Volume No. 32(5) Page 1470