Vinorelbine Tartrate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₄₅H₅₄N₄O₈ · 2C₄H₆O₆              1079.11

8'-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) CAS RN^®: 125317-39-7; UNII: 253GQW851Q.

1 DEFINITION

Vinorelbine Tartrate contains NLT 98.0% and NMT 102.0% 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.]

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K_{▲(CN 1-MAY-2020)}

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

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C.

Sample solution: Equivalent to 15 mg/mL of tartaric acid in water

Analysis: Το 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 5-10 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).

3 ASSAY

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.

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, 3,6-epoxy vinorelbine.

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 x 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between vinorelbine and vinorelbine related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 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 = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of vinorelbine from the Sample solution

r_S = peak response of vinorelbine from the Standard solution

C_S = concentration of USP Vinorelbine Tartrate RS in the Standard solution (mg/mL)

C_U = concentration of Vinorelbine Tartrate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 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 µg/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 = (r_U/r_T) x 100

r_U = peak response for each impurity from the Sample solution

r_T = sum of the responses of all the peaks from the Sample solution

Acceptance criteria: See Table 1.

[NOTE-Disregard 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

^a 3',4',7,8-Tetradehydro-3,4'-dideoxy-3,6-epoxy-6,7-dihydro-8'-norvincaleukoblastine.

^b 4-O-Deacetylvinorelbine.

^c Any individual impurity or coeluted impurities comprising an individual peak.

^d Excluding 3,6-epoxy vinorelbine.

5 SPECIFIC TESTS

5.1 CLARITY OF SOLUTION

Sample solution: Equivalent to 10 mg/mL of anhydrous vinorelbine in water from Vinorelbine Tartrate

Acceptance criteria: The solution is clear.

5.2 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

5.3 pH (791)

3.3-3.8, in a 10-mg/mL solution

5.4 WATER DETERMINATION, Method la(921)

NMT 4.0%

6 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

4-0-Deacetylvinorelbine tartrate.

C₄₃H₅₂N₄O₇ · 2C₄H₆O₆        1037.07

USP Vinorelbine Tartrate RS