Chlorambucil Tablets

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 

Chlorambucil Tablets contain NLT 85.0% and NMT 110.0% of the labeled amount of chlorambucil (C₁₄H₁₉Cl₂NO₂).  

2 IDENTIFICATION 

Change to read: 

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

Sample solution: Shake a quantity of finely powdered Tablets, equivalent to 16 mg of chlorambucil, with 20 mL of carbon disulfide. Filter, evaporate to dryness, and dissolve the residue in 2 mL of carbon disulfide. 

Cell: 1 mm 

Acceptance criteria: Meet the requirements 

3 ASSAY 

Procedure 

Mobile phase: Mix 500 mL of alcohol with 1.0 mL of glacial acetic acid. Dilute with water to 1 L. Degas the solution at a pressure of approximately 250 mm of mercury for 2 min. [Note—The alcohol concentration may be varied to meet system suitability requirements and to provide a suitable elution time for chlorambucil.] 

Internal standard solution: 0.4 mg/mL of USP Propylparaben RS in alcohol 

Standard stock solution: 1 mg/mL of USP Chlorambucil RS in alcohol 

Standard solution: 0.02 mg/mL of USP Chlorambucil RS in alcohol prepared as follows. Transfer 2.0 mL of the Standard stock solution into a 100-mL volumetric flask containing 50 mL of alcohol and, while gently swirling, add 5.0 mL of 0.1 N hydrochloric acid and 2.0 mL of Internal standard solution. Dilute with alcohol to volume. 

Sample solution: Nominally 0.02 mg/mL of chlorambucil in alcohol prepared as follows. Transfer finely powdered Tablets (NLT 20), equivalent to 2 mg of chlorambucil, into a 100-mL volumetric flask containing 50 mL of alcohol and, while gently swirling, add 5.0 mL of 0.1 N hydrochloric acid and 2.0 mL of Internal standard solution. Sonicate for 5 min, and dilute with alcohol to volume. Filter through a medium pore size, sintered-glass filtering funnel, maintaining reduced pressure for the minimum necessary time to avoid solvent loss from evaporation. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 25- or 30-cm × 2-mm; 5- to 10-µm packing L1 

Flow rate: Capable of giving the required Resolution in Suitability requirements and a suitable elution time 

Injection volume: 10–12 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Resolution: NLT 2.0 between the propylparaben and chlorambucil peaks 

Relative standard deviation: NMT 2.0% for 6–8 injections, for the peak response ratio of chlorambucil to propylparaben Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of chlorambucil (C₁₄H₁₉Cl₂NO₂) in the portion of Tablets taken: 

Result = (R_U/R_S) × (C_S/C_U) × 100 

R_U = peak response ratio of chlorambucil to propylparaben from the Sample solution 

R_S = peak response ratio of chlorambucil to propylparaben from the Standard solution 

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

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

Acceptance criteria: 85.0%–110.0% 

4 PERFORMANCE TESTS 

Disintegration 〈701〉 

Analysis: Place 1 Tablet in each of the six tubes of the Blasket, and if the Tablet has a soluble external coating, immerse the basket in water at room temperature for 5 min. Operate the apparatus, using simulated gastric uid TS maintained at 37 ± 2° as the immersion uid. After 30 min of operation in simulated gastric uid TS, lift the basket from the uid, and observe the Tablets. If the Tablets have not disintegrated completely, substitute simulated intestinal uid TS maintained at 37 ± 2° as the immersion uid, and continue the test for a total period of time equal to 45 min, including previous exposure to water and simulated gastric uid TS. Lift the basket from the uid, and observe the Tablets. 

Acceptance criteria: All of the Tablets have disintegrated completely. If 1 or 2 Tablets fail to disintegrate completely, repeat the test on 12 additional Tablets: NLT 16 of the total of 18 Tablets tested disintegrate completely. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve coated Tablets in well-closed containers. Preserve uncoated Tablets in well-closed, light-resistant containers. USP Reference Standards 〈11〉 

USP Chlorambucil RS 

USP Propylparaben RS