Degradation and disposal of some antineoplastic drugs

J Pharm Sci. 1989 Aug;78(8):652-9. doi: 10.1002/jps.2600780811.

Abstract

Bulk quantities and pharmaceutical preparations of the antineoplastic drugs carmustine (BCNU), lomustine (CCNU), chlorozotocin, N-[2-chloroethyl]-N'-[2,6-dioxo-3-piperidinyl]-N-nitrosourea (PCNU), methyl CCNU, mechlorethamine, melphalan, chlorambucil, cyclophosphamide, ifosfamide, uracil mustard, and spiromustine may be degraded using nickel-aluminum alloy in KOH solution. The drugs are completely destroyed and only nonmutagenic reaction mixtures are produced. Destruction of cyclophosphamide in tablets requires refluxing in HCl before the nickel-aluminum alloy reduction. Streptozotocin, chlorambucil, and mechlorethamine may be degraded using an excess of saturated sodium bicarbonate solution. The nitrosourea drugs BCNU, CCNU, chlorozotocin, PCNU, methyl CCNU, and streptozotocin were also degraded using hydrogen bromide in glacial acetic acid. The drugs were completely destroyed but some of the reaction mixtures were mutagenic and the products were found to be, in some instances, the corresponding mutagenic, denitrosated compounds.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetates
  • Aluminum
  • Animals
  • Antineoplastic Agents / analysis*
  • Antineoplastic Agents / toxicity
  • Bicarbonates
  • Chemical Phenomena
  • Chemistry
  • Chromatography, High Pressure Liquid
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Mechlorethamine / analysis
  • Mutagenicity Tests
  • Mutagens
  • Nickel
  • Nitrosourea Compounds / analysis
  • Nitrosourea Compounds / toxicity
  • Oxidation-Reduction
  • Rats
  • Salmonella / genetics
  • Sodium
  • Sodium Bicarbonate
  • Thiosulfates

Substances

  • Acetates
  • Antineoplastic Agents
  • Bicarbonates
  • Mutagens
  • Nitrosourea Compounds
  • Thiosulfates
  • Mechlorethamine
  • Nickel
  • Sodium Bicarbonate
  • Sodium
  • Aluminum