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Vinorelbine Tartrate
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C45H54N4O8·2C4H6O6 1079.11
C¢-Norvincaleukoblastine, 3¢,4¢-didehydro-4¢-deoxy-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:2) (salt).
3¢,4¢-Didehydro-4¢-deoxy-8¢-norvincaleukoblastine L-(+)-tartrate (1:2) (salt) [125317-39-7].
» Vinorelbine Tartrate contains not less than 98.0 percent and not more than 102.0 percent of C45H54N4O8·2C4H6O6, calculated on the anhydrous basis.
Caution—Vinorelbine Tartrate is cytotoxic. Great care should be taken to prevent inhaling particles and exposing the skin to it.
Packaging and storage— Preserve in tight, light-resistant containers. Store in a freezer.
Clarity of solution— Dissolve an amount of Vinorelbine Tartrate, equivalent to 100.0 mg of anhydrous vinorelbine, in 10 mL of water: the solution is clear.
Color of solution— The absorbance of the solution prepared under Clarity of solution, determined in a 1-cm cell at 420 nm in a suitable spectrophotometer, using water as the blank, is not more than 0.03.
A: Infrared Absorption 197K
Test specimen— Dissolve 10 mg in 5 mL of water, add 0.5 mL of 5 N sodium hydroxide, and extract with 5 mL of methylene chloride. Filter the organic extract through anhydrous sodium sulfate, and evaporate the organic extract to a volume of about 0.5 mL.
B: The retention time of the major peak in the chromatogram of the Test solution corresponds to that in the chromatogram of the Diluted standard solution, as obtained in the test for Related compounds.
C: To 0.1 mL of a solution containing the equivalent of about 15 mg of tartaric acid per mL, add 0.1 mL of a 100 g per L solution of potassium bromide, 0.1 mL of a 20 g per L solution of resorcinol, and 3 mL of sulfuric acid. Heat on a hot water bath for 5 to 10 minutes until a dark blue color develops. Allow to cool, and pour the solution into water. The color changes to red (presence of tartrate).
pH 791: between 3.3 and 3.8, in a solution (10 mg per mL).
Water, Method Ia 921: not more than 4.0%.
Residue on ignition 281: not more than 0.1%.
Related compounds—
Phosphate buffer— Dissolve 6.9 g of monobasic sodium phosphate in 900 mL of water. Adjust with phosphoric acid to a pH of 4.2, dilute with water to 1000 mL, and mix.
Mobile phase— Dissolve 1.22 g of sodium 1-decanesulfonate in 620 mL of methanol. Add 380 mL of Phosphate buffer, mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve accurately weighed quantities of USP Vinorelbine Tartrate RS and USP Vinorelbine Related Compound A RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having known concentrations of about 1.4 mg per mL and 0.01 mg per mL, respectively. Expose a portion of this solution in a suitable xenon lamp apparatus capable of supplying a dose of 1600 KJ/m2 between 310 and 800 nm at a power of 500 W/m2 for about one hour, in order to generate an additional degradation product (3¢,4¢,7,8-tetradehydro-3,4¢-dideoxy-3,6-epoxy-6,7-dihydro-C¢-norvincaleukoblastine) having a relative retention time of about 0.8.
Standard solution— Dissolve an accurately weighed quantity of USP Vinorelbine Tartrate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 1.4 mg per mL.
Diluted standard solution— Transfer 1.0 mL of the Standard solution to a 50-mL volumetric flask, and dilute with Mobile phase to volume. Pipet 1.0 mL of this solution into a 100-mL volumetric flask, and dilute with Mobile phase to volume.
Test solution— Transfer about 35 mg of Vinorelbine Tartrate, accurately weighed, to a 25-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 267-nm detector and a 3.9-mm × 15-cm column that contains 5-µm packing L1. The column temperature is maintained at 40. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the retention time for vinorelbine is about 13.5 minutes; and the relative retention times are about 0.8 for the photodegradation product, 1.0 for vinorelbine, and 1.2 for vinorelbine related compound A. The relative retention, , between vinorelbine tartrate and vinorelbine related compound A is not less than 1.1.
Procedure— Separately inject equal volumes (about 20 µL) of the Test solution and the Diluted standard solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Record the chromatograms for three times the retention time of the vinorelbine peak. Disregard any peaks with an area less than or equal to one-half of the area of the peak obtained for vinorelbine in the Diluted standard solution. Calculate the percentage of each impurity in the portion of Vinorelbine Tartrate taken by the formula:
100(ri / rs),
in which ri is the peak response for each impurity obtained from the Test solution; and rs is the sum of the responses of all the peaks: not more than 0.3% of the photodegradation product is found; not more than 0.2% of any individual impurity or coeluted impurities comprising an individual peak is found; and not more than 0.7% of total impurities, excluding the photodegradation product, is found.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 350 mg of Vinorelbine Tartrate, accurately weighed, in 40.0 mL of glacial acetic acid. Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically, using suitable electrodes. Perform a blank determination, and make any necessary correction (see Titrimetry 541). Each mL of 0.1 N perchloric acid is equivalent to 53.96 mg of C45H54N4O8·2C4H6O6.
Auxiliary Information— Staff Liaison : Feiwen Mao, M.S., Senior Scientific Associate
Expert Committee : (MDOOD05) Monograph Development-Ophthalmics Oncologics and Dermatologicals
USP29–NF24 Page 2256
Pharmacopeial Forum : Volume No. 27(5) Page 3054
Phone Number : 1-301-816-8320