Carboplatin

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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C₆H₁₂N₂O₄Pt     371.25

Platinum, diammine[1,1-cyclobutanedicarboxylato(2-)- O,O']-, (SP-4-2);

cis-Diammine(1,1-cyclobutanedicarboxylato)platinum CAS RN®: 41575-94-4; UNII: BG3F62OND5.

1 DEFINITION

Carboplatin contains NLT 98.0% and NMT 102.0% of carboplatin (C₆H₁₂N₂O₄Pt), calculated on the dried basis.

[Caution—Great care should be taken in handling Carboplatin because it is a suspected carcinogen.]

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K

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

Procedure

Mobile phase: Acetonitrile and water (87:13)

Standard solution: 1 mg/mL of USP Carboplatin RS in water. Use it within 2 h.

Sample solution: 1 mg/mL of Carboplatin in water. Use it within 2 h.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 25-cm; 5-μm packing L8

Flow rate: 2.0 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 1.2%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carboplatin (C₆H₁₂N₂O₄Pt) in the portion of Carboplatin taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 OTHER COMPONENTS

Platinum Content

Sample: 0.2 g of Carboplatin, from Loss on Drying

Analysis: Ignite the Sample to constant weight at 800 ± 50°, and weigh the residue. The residue is platinum.

Calculate the platinum content in the portion of Carboplatin taken:

Result = (W_U/W_S) × 100

W_U = weight of platinum

W_S = weight of Sample

Acceptance criteria: 52.0%–53.0% on the dried basis

5 IMPURITIES

Change to read:

Limit of 1,1-Cyclobutanedicarboxylic Acid

Solution A: Dissolve 8.5 g of tetrabutylammonium hydrogen sulfate in 80 mL of water. Add 3.4 mL of phosphoric acid, and adjust with 10 N sodium hydroxide to a pH of 7.55.

Mobile phase: Acetonitrile, Solution A, and water (100:20:880)

Standard solution: 5 μg/mL of 1,1-cyclobutanedicarboxylic acid in Mobile phase

System suitability solution: 2.5 μg/mL of 1,1-cyclobutanedicarboxylic acid and 0.5 mg/mL of Carboplatin in Mobile phase prepared as follows. Mix 1.0 mL of Standard solution with 1.0 mL of Standard solution in the Assay.

Sample solution: 1 mg/mL of Carboplatin in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 3.9-mm (ERR 1-Jan-2022) × 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 100 μL

System suitability

Sample: System suitability solution

[Note—The relative retention times for carboplatin and 1,1-cyclobutanedicarboxylic acid are 0.65 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.5 between the carboplatin and 1,1-cyclobutanedicarboxylic acid peaks

Relative standard deviation: NMT 10%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 1,1-cyclobutanedicarboxylic acid in the portion of Carboplatin taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of 1,1-cyclobutanedicarboxylic acid from the Sample solution

r_S = peak response of 1,1-cyclobutanedicarboxylic acid from the Standard solution

C_S = concentration of 1,1-cyclobutanedicarboxylic acid in the Standard solution (mg/mL)

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

Acceptance criteria: NMT 0.5%

Organic Impurities

Mobile phase, Standard solution, Sample solution, and System suitability: Proceed as directed in the Assay.

Diluted standard solution: 2.5 μg/mL of USP Carboplatin RS in water, from the Standard solution

Chromatographic system: Proceed as directed in the Assay, and the run time is at least 2.5 times the retention time of the carboplatin peak.

Analysis

Samples: Sample solution and Diluted standard solution

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

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of carboplatin from the Diluted standard solution

C_S = concentration of USP Carboplatin RS in the Diluted standard solution (mg/mL)

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

Acceptance criteria: See Table 1. Disregard any peak less than 0.05%.

Table 1

^a cis-Diamminedichloroplatinum(II).

6 SPECIFIC TESTS

Crystallinity 〈695〉: Meets the requirements

pH 〈791〉

Sample solution: 10 mg/mL in water

Acceptance criteria: 5.0–7.0

Loss on Drying 〈731〉

Sample: 1 g

Analysis: Dry the Sample at 105° to constant weight.

Acceptance criteria: NMT 0.5%

Transmittance

Sample solution: 10 mg/mL of Carboplatin in water

Analysis: Determine the percent transmittance in 1-cm cells at a wavelength of 440 nm, using water as the blank.

Acceptance criteria: NLT 97%

Water-Insoluble Matter

Sample: 1 g

Analysis: Transfer the Sample to a 150-mL beaker. Add 100 mL of water, and dissolve by stirring with a stirring bar for 30 min. With the aid of suction, pass through a tared filtering crucible. Rinse the beaker with water, and transfer the rinsings to the crucible. Dry the crucible at 130 ± 10° to constant weight.

Acceptance criteria: NMT 0.5%

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at room temperature.

USP Reference Standards 〈11〉

USP Carboplatin RS