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USP 35
USP Vincristine Sulfate RS USP Vincristine Sulfate (Assay) RS(RB 1-Jul-2011)

Official Monographs / Vinorelbine 5027

System suitability solution: Prepare a solution containing 1.4 mg/mL of USP Vinorelbine Tartrate RS and 0.01 mg/mL of USP Vinorelbine Related Compound A RS in water. 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 1 h to generate an additional photodegradation product, v3,6-epoxy vinorelbine.vUSP35 Standard solution: 1.4 mg/mL of USP Vinorelbine Tartrate RS in Mobile phase Sample solution: 1.4 mg/mL of Vinorelbine Tartrate in Mobile phase Chromatographic system (See Chromatography 621, System Suitability.) Mode: LC Detector: UV 267 nm Column: 3.9-mm 15-cm; 5-m packing L1 Column temperature: 40 Flow rate: 1 mL/min Injection size: 20 L System suitability Samples: System suitability solution and Standard solution Suitability requirements vResolution: NLT 1.5 vUSP35 between vinorelbine and vinorelbine related compound A, System suitability solution vTailing factor: NMT 2.0, Standard solution vUSP35 Relative standard deviation: NLT 2.0%, Standard solution Analysis Samples: Standard solution and Sample solution Calculate the percentage of vinorelbine tartrate (C45H54N4O8 2C4H6O6 ) in the portion of Vinorelbine Tartrate taken: Result = (rU/rS) (CS/CU) 100 = peak response of vinorelbine from the Sample solution rS = peak response of vinorelbine from the Standard solution CS = concentration of USP Vinorelbine Tartrate RS in the Standard solution (mg/mL) CU = concentration of Vinorelbine Tartrate in the Sample solution (mg/mL) Acceptance criteria: 98.0%102.0% on the anhydrous basis IMPURITIES RESIDUE ON IGNITION 281: NMT 0.1% Change to read: ORGANIC IMPURITIES Buffer, Mobile phase, System suitability solution, Sample solution, and System suitability: Proceed as directed in the Assay. Standard stock solution: Use the Standard solution as prepared in the Assay. Standard solution: 0.28 g/mL of vinorelbine tartrate in Mobile phase, from Standard stock solution Chromatographic system: Proceed as directed in the Assay, except use a run time of NLT three times the retention time of vinorelbine. Analysis Samples: Standard solution and Sample solution Calculate the percentage of each impurity in the portion of Vinorelbine Tartrate taken: Result = (rU/rT) 100 rU rT = peak response for each impurity from the Sample solution = sum of the responses of all the peaks from the Sample solution rU

Vinorelbine Tartrate
Change to read:

C45H54N4O8 2C4H6O6 1079.11 v8-Norvincaleukoblastine,3,4-didehydro-4-deoxy-,[R-(R*,R*)]2,3-dihydroxybutanedioate (1:2) (salt);vUSP35 3,4-Didehydro-4-deoxy-8-norvincaleukoblastine L-(+)-tartrate (1:2) (salt) [125317-39-7]. DEFINITION Vinorelbine Tartrate contains NLT 98.0% and NMT 102.0% of C45H54N4O8 2C4H6O6, calculated on the anhydrous basis. [CAUTIONVinorelbine Tartrate is cytotoxic. Great care should be taken to prevent inhaling particles and exposing the skin to it.] IDENTIFICATION A. INFRARED ABSORPTION 197K Sample: 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. Acceptance criteria: Meets the requirements Change to read: B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the vAssay.vUSP35 C. Sample solution: Equivalent to 15 mg/mL of tartaric acid in water Analysis: To 0.1 mL of the Sample solution add 0.1 mL of 100 mg/mL of potassium bromide, 0.1 mL of 20 mg/mL of resorcinol, and 3 mL of sulfuric acid. Heat on a hot water bath for 510 min until a dark blue color develops. Allow to cool, and pour the solution into water. Acceptance criteria: The color changes to red (presence of tartrate). ASSAY Change to read: PROCEDURE Buffer: Dissolve 6.9 g of monobasic sodium phosphate in 900 mL of water. Adjust with phosphoric acid to a pH of 4.2, and dilute with water to 1000 mL. Mobile phase: Dissolve 1.22 g of sodium 1-decanesulfonate in 620 mL of methanol, and add 380 mL of Buffer.

Official from August 1, 2012 Copyright (c) 2012 The United States Pharmacopeial Convention. All rights reserved.

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5028 Vinorelbine / Official Monographs

Acceptance criteria: See Table 1. [NOTEDisregard any peaks with an area less than or equal to one-half of the area of the peak for vinorelbine in the Standard solution.]
Table 1 Relative Retention Time 0.8 1.0 1.2 Acceptance Criteria, NMT (%) 0.3 0.2 0.2 0.7

USP 35
Clarity and color of solutionThe solution of Injection (10 mg per mL) is clear. The absorbance of a solution of Injection, determined in a 1-cm cell at 420 nm, with a suitable spectrophotometer, using water as the blank, is not greater than 0.060. IdentificationThe retention time and the UV spectrum of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay. Bacterial endotoxins 85It contains not more than 3.0 USP Endotoxin units per mg of vinorelbine. Sterility 71It meets the requirements when tested as directed for Membrane Filtration under Test for Sterility of the Product to be Examined. pH 791: between 3.3 and 3.8. Particulate matter 788: meets the requirements for smallvolume injections. Related compounds Mobile phase and System suitability solutionProceed as directed in the Assay under Vinorelbine Tartrate. Standard solution and Diluted standard solutionProceed as directed in the test for Related compounds under Vinorelbine Tartrate. Chromatographic systemProceed as directed in the Assay. Test solutionDilute a portion of Injection with Mobile phase to obtain a solution containing 1.0 mg of vinorelbine per mL. ProcedureProceed as directed for Procedure in the test for Related compounds under Vinorelbine Tartrate. Not more than 1.0% of the photodegradation product is found; not more than 0.3% of vinorelbine related compound A is found; not more than 0.2% of any other individual impurity is found; and the sum of all impurities, excluding any peaks that are below the limit of quantitation (0.02%), is not more than 2.0%. Other requirementsIt meets the requirements under Injections 1. Assay Phosphate buffer, Mobile phase, and System suitability solutionProceed as directed in the Assay under Vinorelbine Tartrate. Standard preparationDissolve an accurately weighed quantity of USP Vinorelbine Tartrate RS in water to obtain a solution having a known concentration of about 0.14 mg per mL. Assay preparationTransfer an accurately measured volume of Injection, equivalent to about 10 mg of vinorelbine, to a 100-mL volumetric flask, dilute with water to volume, and mix. Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a diode-array detector and a 3.9-mm 15-cm column that contains 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 relative retention, r, between vinorelbine tartrate and vinorelbine related compound A is not less than 1.1. [NOTEFor peak identification purposes, the relative retention times are about 0.8 for the photodegradation product, 1.0 for vinorelbine, and 1.2 for vinorelbine related compound A.] ProcedureSeparately inject equal volumes (about 20 L) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the vinorelbine peaks, using a diode-array detector. Calculate the quantity, in mg, of vinorelbine (C45H54N4O8) in each mL of the Injection taken by the formula: (778.93/1079.11)C(L/D)(rU / rS) in which 778.93 and 1079.11 are the molecular weights of vinorelbine and vinorelbine tartrate, respectively; C is the concentration, in mg per mL, of USP Vinorelbine Tartrate RS in the Standard preparation; L is the labeled quantity, in mg, of vinorelbine in each mL of Injection taken; D is the concentration, in mg per mL, of vinorelbine in the Assay preparation; and rU

Name 3,6-Epoxy vinorelbinea Vinorelbine Vinorelbine related compound Ab Any unspecified impurityc Total Impuritiesd

a v3,4,7,8-Tetradehydro-3,4-dideoxy-3,6-epoxy-6,7-dihydro-8-

norvincaleukoblastine.vUSP35 b 4-O-Deacetylvinorelbine. c Any individual impurity or coeluted impurities comprising an individual peak. d Excluding 3,6-epoxy vinorelbine.

SPECIFIC TESTS CLARITY OF SOLUTION Sample solution: Equivalent to 10 mg/mL of anhydrous vinorelbine in water from Vinorelbine Tartrate Acceptance criteria: The solution is clear. COLOR OF SOLUTION Sample solution: Equivalent to 10 mg/mL of anhydrous vinorelbine in water from Vinorelbine Tartrate Analysis: Determine the absorbance of the Sample solution in a 1-cm cell at 420 nm in a suitable spectrophotometer, using water as the blank. Acceptance criteria: NMT 0.03 PH 791: 3.33.8, in a 10-mg/mL solution WATER DETERMINATION, Method Ia 921: NMT 4.0% ADDITIONAL REQUIREMENTS PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store in a freezer. USP REFERENCE STANDARDS 11 USP Vinorelbine Related Compound A RS 4-O-Deacetylvinorelbine. C43H52N4O7 2C4H6O6 1037.07 USP Vinorelbine Tartrate RS

Vinorelbine Injection
Vinorelbine Injection is a sterile solution of Vinorelbine Tartrate in Water for Injection. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of vinorelbine (C45H54N4O8). CautionHandle Vinorelbine Injection with great care because it is a potent cytotoxic agent.
Packaging and storagePreserve in single-dose Containers for Injections as described under Injections 1, preferably of Type I glass, protected from light. Store in a refrigerator. USP Reference standards 11 USP Endotoxin RS USP Vinorelbine Related Compound A RS 4-O-Deacetylvinorelbine. C43H52N4O7 2C4H6O6 1037.07 USP Vinorelbine Tartrate RS

Official from August 1, 2012 Copyright (c) 2012 The United States Pharmacopeial Convention. All rights reserved.