Vinblastine Sulfate
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C46H58N4O9.H2SO4 909.07

Vincaleukoblastine,sulfate (1:1)(salt).
Vincaleukoblastine sulfate (1:1)(salt) [143-67-9].
»Vinblastine Sulfate contains not less than 96.0percent and not more than 102.0percent of C46H58N4O9.H2SO4,corrections being applied for loss in weight.
Caution—Handle Vinblastine Sulfate with great care since it is a potent cytotoxic agent.
Packaging and storage— Preserve in tight,light-resistant containers,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.
Identification—
A: Infrared Absorption á197Kñ—The test specimen and Reference Standard are previously dried in vacuum at 60for 16hours.
B: Asolution (1in 10)responds to the test for Sulfate á191ñ.
pHá791ñ: between 3.5and 5.0,in a solution prepared by dissolving 3mg in 2mLof water.
Loss on drying (see Thermal Analysis á891ñ)—[NOTE—In this procedure,perform weighings rapidly with minimum exposure of the substances to air.]Determine the percentage of volatile substances by thermogravimetric analysis on an appropriately calibrated instrument,using about 10mg of Vinblastine Sulfate,accurately weighed.Heat the specimen at the rate of 5per minute between ambient temperature and 200in an atmosphere of nitrogen at a flow rate of 40mLper minute.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):it loses not more than 15.0%of its weight.
Related compounds—
Mobile phase ,System suitability preparation,and Chromatographic system—Prepare as directed in the Assay.
High load test preparation— Prepare as directed for Assay preparationin the Assay.
Low load test preparation— Pipet 1mLof High load test preparationinto a 25-mLvolumetric flask,dilute with water to volume,and mix.
Procedure— Separately inject 200µLof the Low load test preparationand of the High load test preparationinto the chromatograph,and record the chromatograms.Measure the peak responses,ri,of any related substances appearing after the solvent peak in the chromatogram of the High load test preparation.Calculate the total percentage of responses due to related substances taken by the formula:
100rt/(rt+25rv),
in which rt is the sum of the ri responses;and rvis the vinblastine peak response in the chromatogram of the Low load test preparation.Not more than 3.0%is found.Calculate the percentage response of each related substance taken by the formula:
100ri/(rt+25rv).
Not more than 1.0%of response due to any individual related substance is found.
Other requirements— Where the label states that Vinblastine Sulfate is sterile,it meets the requirements for Sterilityand Bacterial endotoxinsunder Vinblastine Sulfate for Injection.Where the label states that Vinblastine Sulfate must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Vinblastine Sulfate for Injection.
Assay—
Mobile phase— Mix 14mLof diethylamine with 986mLof water,and adjust with phosphoric acid to a pHof 7.5(Solution A).Mix 200mLof acetonitrile with 800mLof methanol (Solution B).Mix 380mLof Solution Awith 620mLof Solution B,pass through a 0.5-µm filter,and degas under vacuum.The ratio of Solutions Aand Bmay be varied to meet system suitability requirements and to provide a suitable elution time for vinblastine sulfate.
Standard preparation— Dissolve an accurately weighed quantity of USP Vinblastine Sulfate RSin water to obtain a solution having a known concentration of about 0.4mg per mL.
Assay preparation— Transfer about 4mg of Vinblastine Sulfate,accurately weighed,to a 10-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.
System suitability preparation— Dissolve an amount of USP Vincristine Sulfate RSin a portion of Standard preparationto obtain a solution having concentrations of about 0.4mg of each Reference Standard per mL.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 262-nm detector,a pre-column packed with porous silica gel installed between the pump and the injector,and a 4.6-mm ×15-cm analytical column that contains packing L1.The Mobile phaseis maintained at a pressure and flow rate (about 2mLper minute)capable of producing the required resolution and a suitable elution time.Chromatograph replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%.Similarly chromatograph 20µLof the System suitability preparation,and record the peak responses:the resolution,R,between the vincristine and vinblastine is not less than 4.0.[NOTE—For a particular column,the resolution may be increased by increasing the proportion of Solution Ain the Mobile phase.]
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparation into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C46H58N4O9.H2SO4in the portion of Vinblastine Sulfate taken by the formula:
10C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Vinblastine Sulfate RS(corrected for loss in weight)in the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 2024
Phone Number:1-301-816-8389
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