Chlorambucil

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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C₁₄H₁₉Cl₂NO₂ 304.21 

Benzenebutanoic acid, 4-[bis(2-chloroethyl)amino]-; 

4-[p-[Bis(2-chloroethyl)amino]phenyl]butyric acid CAS RN®: 305-03-3; UNII: 18D0SL7309. 

1 DEFINITION 

Chlorambucil contains NLT 98.0% and NMT 101.0% of chlorambucil (C₁₄H₁₉Cl₂NO₂), calculated on the anhydrous basis.  

[Caution—Great care should be taken to prevent inhaling particles of Chlorambucil and exposing the skin to it.] 

2 IDENTIFICATION

Change to read: 

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

Sample solution: 8 mg/mL in carbon disulfide 

Cell: 1 mm 

Acceptance criteria: Meets the requirements 

B. 

Sample solution: Dissolve 50 mg of Chlorambucil in 5 mL of acetone, and dilute with water to 10 mL. 

Analysis: To the Sample solution add 1 drop of 2 N sulfuric acid, then add 4 drops of silver nitrate TS. 

Acceptance criteria: No opalescence is observed immediately (absence of chloride ion). Warm the solution on a steam bath: opalescence develops (presence of ionizable chlorine). 

3 ASSAY 

Procedure 

Sample: 200 mg of Chlorambucil 

Titrimetric system 

Mode: Direct titration 

Titrant: 0.1 N sodium hydroxide VS 

Endpoint detection: Visual 

Analysis: Dissolve the Sample in 10 mL of acetone, add 10 mL of water, and titrate with Titrant, using phenolphthalein TS as the indicator. Each mL of 0.1 N sodium hydroxide is equivalent to 30.42 mg of chlorambucil (C₁₄H₁₉Cl₂NO₂). 

Acceptance criteria: 98.0%–101.0% on the anhydrous basis 

4 SPECIFIC TESTS 

Melting Range or Temperature 〈741〉: 65°–69° 

Water Determination, Method I〈921〉: NMT 0.5% 

5 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight, light-resistant containers. 

USP Reference Standards 〈11〉 

USP Chlorambucil RS