Vincristine Sulfate
(RB 1-Jul-2011)
C46H56N4O10·H2SO4 923.04
Vincaleukoblastine, 22-oxo-, sulfate (1:1) (salt);
Leurocristine sulfate (1:1) (salt)
[2068-78-2].
197K
Standard:
Proceed as directed in the chapter using either USP Vincristine Sulfate RS or USP Vincristine Sulfate (Assay) RS. If USP Vincristine Sulfate (Assay) RS is used, dissolve a portion of it in a mixture of methylene chloride and methanol (3:1). Transfer the supernatant to an open container, and evaporate it at room temperature under nitrogen.
11
USP Vincristine Sulfate (Assay) RS
(RB 1-Jul-2011)
(vin kris' teen sul' fate).
Change to read:
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(RB 1-Jul-2011)C46H56N4O10·H2SO4 923.04
Vincaleukoblastine, 22-oxo-, sulfate (1:1) (salt);
Leurocristine sulfate (1:1) (salt)
[2068-78-2].DEFINITION
Vincristine Sulfate contains NLT 95.0% and NMT 105.0% of C46H56N4O10·H2SO4, calculated on the dried basis.
[Caution—Handle Vincristine Sulfate with great care because it is a potent cytotoxic agent.
]
IDENTIFICATION
Change to read:
• A. Infrared Absorption 197K
Standard:
Proceed as directed in the chapter using either USP Vincristine Sulfate RS or USP Vincristine Sulfate (Assay) RS. If USP Vincristine Sulfate (Assay) RS is used, dissolve a portion of it in a mixture of methylene chloride and methanol (3:1). Transfer the supernatant to an open container, and evaporate it at room temperature under nitrogen.
Acceptance criteria:
Meets the requirements(RB 1-Jul-2011)
(RB 1-Jul-2011)
• B. Identification Tests—General, Sulfate 191
191
Sample solution:
100 mg/mL
Acceptance criteria:
Meets the requirements
ASSAY
Change to read:
• 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(RB 1-Jul-2011) of USP Vincristine Sulfate RS or Vincristine Sulfate (Assay) RS(RB 1-Jul-2011) in water
1.2 mg/mL(RB 1-Jul-2011) of USP Vincristine Sulfate RS or Vincristine Sulfate (Assay) RS(RB 1-Jul-2011) in water
System suitability solution:
1 mg/mL of (RB 1-Jul-2011) USP Vinblastine Sulfate RS in the Standard solution(RB 1-Jul-2011)
(RB 1-Jul-2011) USP Vinblastine Sulfate RS in the Standard solution(RB 1-Jul-2011)
Sample solution:
1.2 mg/mL(RB 1-Jul-2011) 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 as directed for USP Vincristine Sulfate RS.
1.2 mg/mL(RB 1-Jul-2011) 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 as directed for USP Vincristine Sulfate RS.
Chromatographic system
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; packing L7
Flow rate:
1.5 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 4.0 between vincristine sulfate and vinblastine sulfate, System suitability solution. [Note—For a particular column, the resolution may be increased by increasing the proportion of water in the Mobile phase. ]
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 from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| CU | = | = concentration of the Sample solution (mg/mL) |
Acceptance criteria:
95.0%–105.0% on the dried basis
IMPURITIES
• 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
| Time (min) |
Solution A
(%) |
Solution B
(%) |
|---|---|---|
| 0 | 38 | 62 |
| 12 | 38 | 62 |
| 27 | 8 | 92 |
| 29 | 38 | 62 |
| 34 | 38 | 62 |
Standard solution, System suitability solution, and System suitability:
Proceed as directed in the Assay.
Sample solution A:
Prepare as directed for the Sample solution in the Assay.
Sample solution B:
0.04 mg/mL of vincristine sulfate from Sample solution A in water
Chromatographic system:
Proceed as directed in the Assay, except use a Flow rate of 2 mL/min and 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 Vincristine Sulfate 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 vincristine from Sample solution B |
Calculate the percentage of total impurities in the portion of Vincristine Sulfate taken:
Result = [SrUA/(SrUA + 25rUB)] × 100
| rUA | = | = peak response of each impurity appearing after the solvent peak from Sample solution A |
| rUB | = | = peak response of vincristine from Sample solution B |
Acceptance criteria
Individual impurities:
NMT 1.0%
Total impurities:
NMT 4.0%
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 (at 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 (at about 160)
Acceptance criteria:
It loses NMT 12.0% of its weight.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store in a freezer.
Change to read:
• USP Reference Standards 11
USP Vinblastine Sulfate RS 
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[Note—No loss on drying determination is needed for USP Vinblastine Sulfate RS. ]
USP Vincristine Sulfate RS
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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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 5022
Pharmacopeial Forum: Volume No. 37(1)