Oxaliplatin Injection

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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1 DEFINITION

Oxaliplatin Injection is a sterile solution of Oxaliplatin in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of oxaliplatin (C₈H₁₄N₂O₄Pt).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970 (OFFICIAL 1-MAY-2020)

Sample solution: 100 µg/mL

Medium: Water

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.

3 ASSAY

3.1 PROCEDURE

[NOTE-All HPLC autosampler vials should be made of polypropylene.]

Acidified water: Adjust water with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Acidified water (1:99)

System suitability solution: 0.1 mg/mL of USP Oxaliplatin RS and 0.1 mg/mL of USP Oxaliplatin System Suitability RS in water. [NOTE-USP

Oxaliplatin System Suitability RS is [SP-4-2-(1R-trans)]-(1,2-cyclohexanediamine-N,N') dichloridoplatinum(II).]

Standard solution: 0.1 mg/mL of USP Oxaliplatin RS in water

Sample solution: Nominally 0.1 mg/mL of oxaliplatin in water from the combined contents of NLT 3 vials of Injection

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

3.3 System suitability

Sample: System suitability solution

[NOTE-The relative retention times for [SP-4-2-(1R-trans)]-(1,2-cyclohexanediamine-N,N') dichloridoplatinum(II) and oxaliplatin are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between [SP-4-2-(1R-trans)]-(1,2-cyclohexanediamine-N,N') dichloridoplatinum(II) and oxaliplatin

Tailing factor: NMT 2.0 for the oxaliplatin peak

Relative standard deviation: NMT 1.0% for the oxaliplatin peak

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of oxaliplatin (C₈H₁₄N₂O₄Pt) in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = nominal concentration of oxaliplatin in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

4.1 LIMIT OF OXALIC ACID

[NOTE-All HPLC autosampler vials should be made of polypropylene.]

Mobile phase: 0.43 g/L of sodium carbonate and 0.04 g/L of sodium bicarbonate in water

Standard stock solution: 0.32 mg/mL of USP Oxaliplatin Related Compound A RS in water. [NOTE-USP Oxaliplatin Related Compound A RS is available as dihydrate oxalic acid.]

Tartaric acid standard stock solution: 0.25 mg/mL of tartaric acid in water

System suitability solution: 23 µg/mL of USP Oxaliplatin Related Compound A RS and 12.5 µg/mL of tartaric acid in water from Standard stock solution and Tartaric acid standard stock solution.

Standard solution: 16.2 µg/mL of USP Oxaliplatin Related Compound A RS in water from Standard stock solution

Sensitivity solution: 1.94 µg/mL USP Oxaliplatin Related Compound A RS in water from Standard solution

Sample solution: Nominally equivalent to 2 mg/mL of oxaliplatin in water from Injection

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: Conductivity with anion suppression. [NOTE-A recycle mode may be used.]

Column: 4.0-mm x 25-cm; packing L81

Autosampler temperature: 5°

Flow rate: 2.0 mL/min

Injection volume: 40 µL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[NOTE-The relative retention times for tartaric acid and oxalic acid are 0.4 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 8 between tartaric acid and oxalic acid, System suitability solution

Tailing factor: 0.5-1.5 for the oxalic acid peak, Standard solution

Relative standard deviation: NMT 3.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxalic acid in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response of oxalic acid from the Sample solution

r_S = peak response of oxalic acid from the Standard solution

C_S = concentration of USP Oxaliplatin Related Compound A RS in the Standard solution (mg/mL)

C_U = nominal concentration of oxaliplatin in the Sample solution (mg/mL)

M_r1 = molecular weight of anhydrous oxalic acid, 90.03

M_r2 = molecular weight of oxaliplatin related compound A, 126.07

Acceptance criteria: NMT 0.6%

4.2 LIMIT OF (SP-4-2)-DIAQUA[(1R,2R)-CYCLOHEXANE-1,2-DIAMINE-N,N']PLATINUM AND UNSPECIFIED IMPURITIES

[NOTE-All HPLC autosampler vials should be made of polypropylene.]

Solution A: Dissolve 1.36 g of monobasic potassium phosphate and 0.55 g of sodium heptanesulfonate in 1 L of water. Adjust with

phosphoric acid to a pH of 3.0.

Solution B: Methanol and Solution A (19:81)

Solution C: Methanol and Solution A (50.5:49.5)

Mobile phase: See Table 1.

Table 1

System suitability solution: 2 mg/mL of USP Oxaliplatin RS in 0.005 M sodium hydroxide. Allow this solution to stand at room temperature for at least 5 days. Transfer 5 mL of this solution into a 50-mL volumetric flask, and dilute with water to volume. [NOTE-The preparation of the System suitability solution forms (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum and diaquodiaminocyclohexaneplatinum dimer.]

Standard stock solution: Transfer a weighed quantity of USP Oxaliplatin Related Compound B RS into a suitable volumetric flask, add a volume of methanol equivalent to about 25% of the final volume, and sonicate for approximately 2 min to disperse the solids. Add a volume of 0.01 M nitric acid equivalent to about 65% of the final volume, and sonicate for approximately 30 min to dissolve. Allow to cool, if necessary, and dilute with 0.01 M nitric acid to volume to obtain a solution with a concentration of 0.125 mg/mL.

Standard solution: 31.25 µg/mL of USP Oxaliplatin Related Compound B RS in 0.01 M nitric acid from the Standard stock solution. [NOTE-USP Oxaliplatin Related Compound B RS is converted to (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum in the Standard solution preparation.]

Sample solution: Combined contents of NLT 3 vials of Injection

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 7.5-cm; 3-µm packing L1

Column temperature: 10°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 8.0 between the peaks of (SP-4-2)-diaqua [(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum and diaquodiaminocyclohexaneplatinum dimer, System suitability solution

Tailing factor: NMT 2.0 for the (SP-4-2)-diaqua [(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum peak, System suitability solution

Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x (1/F) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum from the Standard solution

C_S = concentration of USP Oxaliplatin Related Compound B RS in the Standard solution (mg/mL)

C_U = nominal concentration of oxaliplatin in the Sample solution (mg/mL)

M_r1 = molecular weight of (SP-4-2)-diaqua [(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum, 345.30

M_r2 = molecular weight of oxaliplatin related compound B, 433.28

F = relative response factor for each individual impurity (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a (SP-4-2)-Di-µ-oxobis[(1R,2R)-cyclohexane-1,2-diamine-kN,kN']diplatinum.

^b From the tests for Limit of Oxalic Acid and Limit of (SP-4-2)-Diaqua [(1R,2R)-cyclohexane-1,2-diamine-N,N']platinum and Unspecified Impurities.

5 SPECIFIC TESTS

5.1 BACTERIAL ENDOTOXINS TEST (85)

Meets the requirements

5.2 STERILITY TESTS (71), Test for Sterility of the Product to Be Examined, Membrane Filtration

Meets the requirements

5.3 PH (791)

4.0-7.0 using a polymer combination electrode

5.4 PARTICULATE MATTER IN INJECTIONS (788)

It meets the requirements for small-volume injections.

5.5 OTHER REQUIREMENTS

It meets the requirements in Injections and Implanted Drug Products (1).

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light. Store at controlled room temperature. Do not freeze.

6.2 LABELING

Label it to indicate that it is to be diluted with a 5% dextrose solution. Oxaliplatin Injection must not be diluted in sodium chloride solutions or in chloride-containing solutions.

6.3 USP REFERENCE STANDARDS (11)

USP Oxaliplatin RS

USP Oxaliplatin Related Compound A RS

Oxalic acid dihydrate.

C₂H₂O₄·2H₂O 126.07

USP Oxaliplatin Related Compound B RS

[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N') dinitratoplatinum(II).

C₆H₁₄N₄O₆Pt 433.28

USP Oxaliplatin System Suitability RS

[SP-4-2-(1R-trans)]-(1,2-Cyclohexanediamine-N,N') dichloridoplatinum(II).

C₆H₁₄Cl₂N₂Pt 380.17