Carmustine for Injection
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).
[CautionUse appropriate surgical gloves, arm covers, and a dust mask. Perform all work under a fume hood approved for testing cytotoxic agents when possible.
]
IDENTIFICATION
• A. Infrared Absorption 197F
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.
ASSAY
Change to read:
• Procedure
[NotePrepare 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. [NoteAllow 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
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:
20USP35 µL
System suitability
Sample:
System suitability solution
[NoteThe 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 = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
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 = (rU/rS) × [100 × CS/(CU × A)] × 100
Acceptance criteria
Carmustine related compound A:
NMT 1.0%
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%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve as described in Injections 1, Containers for Sterile Solids at a temperature between 2 and 8.
• Labeling:
It meets the requirements in Injections 1, Labeling.
• Constituted Solution:
At time of use, it meets the requirements in Injections 1, Constituted 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
USP Endotoxin RS
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2506
Pharmacopeial Forum: Volume No. 36(6) Page 1508
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