Carmustine for 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

Carmustine for Injection is a sterile lyophilized preparation of carmustine. It contains NLT 90.0% and NMT 110.0% of the labeled amount of carmustine (C₅H₉Cl₂N₃O₂).

[Caution—Use appropriate surgical gloves, arm covers, and a dust mask. Perform all work under a fume hood approved for testing cytotoxic agents when possible.]

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197F (CN 1-May-2020)

Sample: Melt a small portion of the sample in a suitable container in a controlled water bath or oven, and set the temperature between 33° and 40°.

Standard: A similar preparation of USP Carmustine RS

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

[Note—Prepare solutions in low-actinic glassware, and keep them refrigerated until use.]

Mobile phase: See the gradient table below.

Diluent: Acetonitrile and water (1:3)

Standard stock solution: 2.0 mg/mL of USP Carmustine RS in acetonitrile

Standard solution: 0.2 mg/mL of USP Carmustine RS in Diluent, from Standard stock solution

Impurity standard stock solution: 0.1 mg/mL of USP Carmustine Related Compound A RS in acetonitrile

System suitability solution: 0.2 mg/mL of USP Carmustine RS and 0.002 mg/mL of USP Carmustine Related Compound A RS in Diluent, from the Standard stock solution and Impurity standard stock solution, respectively

Sample stock solution: 2.0 mg/mL of carmustine in acetonitrile, from Carmustine for Injection. [Note—Allow test vials to warm to room temperature in a desiccator for 1 h.]

Sample solution: 0.2 mg/mL of carmustine in Diluent, from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 200 nm

Refrigerated autosampler temperature: 5°

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

Flow rate: 1.5 mL/min

Injection size: 20 μL

System suitability

Sample: System suitability solution

[Note—The relative retention times for carmustine related compound A and carmustine are 0.5 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between carmustine related compound A and carmustine

Tailing factor: NMT 1.5 for the carmustine related compound A and carmustine peaks

Relative standard deviation: NMT 2.0% for the carmustine related compound A and carmustine peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carmustine (C₅H₉Cl₂N₃O₂) in the portion of Carmustine for Injection taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak area of the Sample solution

r_S = peak area of the Standard solution

C_S = concentration of carmustine in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

IMPURITIES

Organic Impurities

Procedure: Limit of Carmustine Related Compound A

Diluent, Impurity standard stock solution, System suitability solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard solution: 0.002 mg/mL of USP Carmustine Related Compound A RS in Diluent, from the Impurity standard stock solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carmustine related compound A in the portion of Carmustine for Injection taken:

Result = (r_U/r_S) × [100 × C_S/(C_U × A)] × 100

r_U = peak response of carmustine related compound A from the Sample solution

r_S = peak response of carmustine related compound A from the Standard solution

C_S = concentration of carmustine related compound A in the Standard solution (mg/mL)

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

A = assay of Carmustine for Injection, as a percentage

Acceptance criteria

Carmustine related compound A: NMT 1.0%

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: NMT 0.95 USP Endotoxin Unit/mg of carmustine

Sterility Tests 〈71〉: Meets the requirements

pH 〈791〉: Between 4.0 and 6.8 in a constituted solution prepared as directed in the labeling

Water Determination, Method I〈921〉: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution at a temperature between 2° and 8°.

Labeling: It meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products.

Constituted Solution: At time of use, it meets the requirements in Injections and Implanted Drug Products 〈1〉, Speciffc Tests, Completeness and clarity of solutions.

USP Reference Standards 〈11〉

USP Carmustine RS

Urea, N,N′-bis(2-chloroethyl)-N-nitroso-;

1,3-Bis(2-chloroethyl)-1-nitrosourea.

C₅H₉Cl₂N₃O₂ 214.05

USP Carmustine Related Compound A RS

1,3-Bis(2-chloroethyl) Urea.

C₅H₁₀Cl₂N₂O 185.05