Carboplatin 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

Carboplatin Injection is a sterile, nonpyrogenic, and aqueous solution of Carboplatin. It contains NLT 90.0% and NMT 110.0% of the labeled amount of carboplatin (C₆H₁₂N₂O₄Pt).

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

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

[Note—Use the solutions containing carboplatin within 2 h of preparation.]

Procedure

Mobile phase: Acetonitrile and water (87:13)

Diluent: Acetonitrile and water (50:50)

Standard solution: 1.0 mg/mL of USP Carboplatin RS in Diluent

Sample solution: Nominally 1.0 mg/mL of carboplatin from Injection in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identi

cation A, use a diode array detector in the range of 200–400 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 2.0

Relative standard deviation: NMT 1.2%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of carboplatin (C₆H₁₂N₂O₄Pt) in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of carboplatin from the Sample solution

r_S = peak response of carboplatin from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Limit of Cyclobutane Dicarboxylic Acid

[Note—Use the solutions containing carboplatin or cyclobutane dicarboxylic acid within 2 h of preparation.]

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 7.6.

Mobile phase: Acetonitrile, Solution A, and water (10:2:88)

System suitability solution: 1.0 mg/mL of USP Carboplatin RS and 4.0 μg/mL of cyclobutane dicarboxylic acid in water

Sensitivity solution: 1.5 μg/mL of cyclobutane dicarboxylic acid in water

Standard solution: 4.0 μg/mL of cyclobutane dicarboxylic acid in water

Sample solution: Nominally 1.0 mg/mL of carboplatin in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 2.0 mL/min

Injection volume: 100 μL

Run time: NLT 2.5 times the retention time of cyclobutane dicarboxylic acid

System suitability

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

[Note—The relative retention times of carboplatin and cyclobutane dicarboxylic acid are 1.0 and 3.0, respectively.]

Suitability requirements

Resolution: NLT 2.5 between carboplatin and cyclobutane dicarboxylic acid, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cyclobutane dicarboxylic acid in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of cyclobutane dicarboxylic acid from the Sample solution

r_S = peak response of cyclobutane dicarboxylic acid from Standard solution

C_S = concentration of cyclobutane dicarboxylic acid in Standard solution (mg/mL)

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

Acceptance criteria: NMT 1.0%

Organic Impurities

[Note—Use the solutions containing carboplatin within 2 h of preparation.]

Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 2.5 times the retention time of carboplatin

System suitability solution: 1.0 mg/mL of USP Carboplatin RS and 2.0 μg/mL of USP Cisplatin RS in Diluent

Sensitivity solution: 1.0 μg/mL of USP Carboplatin RS in Diluent

Standard solution: 2.0 μg/mL each of USP Carboplatin RS and USP Cisplatin RS in Diluent

System suitability

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

Suitability requirements

Resolution: NLT 5.0 between cisplatin and carboplatin, System suitability solution

Relative standard deviation: NMT 5.0% for cisplatin and carboplatin, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cisplatin in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of cisplatin from the Sample solution

r_S = peak response of cisplatin from the Standard solution

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

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

Calculate the percentage of any unspecified degradation product in the portion of Injection taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of any unspecified degradation product from the Sample solution

r_S = peak response of carboplatin from the Standard solution

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

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

Acceptance criteria: See Table 1. The reporting threshold is 0.1%.

Tablet 1

^a Include the amount of Cyclobutane dicarboxylic acid determined in the Limit of Cyclobutane Dicarboxylic Acid test.

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: Meets the requirements

Particulate Matter in Injections 〈788〉: Meets the requirements

pH 〈791〉: 5.0–7.0

Sterility Tests 〈71〉: Meets the requirements

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in multiple-dose containers. Protect from light. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Carboplatin RS

USP Cisplatin RS

Diamminedichloroplatinum.

C₂H₆N₂Pt 300.05 (USP 1-May-2023)