Vinorelbine Tartrate

(vin or' el been tar' trate).

Change to read:

C45H54N4O8·2C4H6O6 1079.11

8¢-Norvincaleukoblastine,3¢,4¢-didehydro-4¢-deoxy-,[R-(R*,R*)]-2,3-dihydroxybutanedioate (1:2) (salt);

USP35
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.

[Caution—Vinorelbine 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

Assay.

USP35

• 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 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).

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.

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.

USP35

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-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

USP35 between vinorelbine and vinorelbine related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

USP35

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

rU	=	= 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 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 = (rU/rT) × 100

rU	=	= peak response for each impurity from the Sample solution
rT	=	= 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

Name	Relative Retention Time	Acceptance Criteria, NMT (%)
3,6-Epoxy vinorelbinea	0.8	0.3
Vinorelbine	1.0	—
Vinorelbine related compound Ab	1.2	0.2
Any unspecified impurityc	—	0.2
Total Impuritiesd	—	0.7
a 3¢,4¢,7,8-Tetradehydro-3,4¢-dideoxy-3,6-epoxy-6,7-dihydro-8¢-norvincaleukoblastine.USP35 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

: 3.3–3.8, 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

USP Vinorelbine Related Compound A RS

4-O-Deacetylvinorelbine.
C43H52N4O7·2C4H6O6 1037.07

USP Vinorelbine Tartrate RS

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 5027

Pharmacopeial Forum: Volume No. 37(1)