Doxorubicin Stability-indicating Method and its Main Degradation Products In vitro Toxicity.

Area of Science:

• Environmental Chemistry
• Pharmaceutical Science
• Toxicology

Background:

• Anthropogenic activities introduce emerging compounds impacting human health and the environment.
• Limited knowledge exists on the toxicity of newly identified or poorly documented compounds.
• Pharmaceuticals and their impurities pose risks due to insufficient understanding of their mechanisms and effects.

Purpose of the Study:

• To evaluate the degradation behavior of doxorubicin (DOX) under stress conditions.
• To identify major degradation pathways and elucidate the structures of DOX degradation products.
• To assess the in vitro toxicity of DOX degradation products.

Main Methods:

• Development and validation of a stability-indicating HPLC-DAD-MS method.
• Exposure of doxorubicin to acid/base hydrolysis, oxidation, photolysis, and thermal stress.
• In vitro toxicity assessment using mononuclear cells.

Main Results:

• Identified degradation products including 7-deoxydehydrodoxorubicinone (acid hydrolysis).
• Characterized a major thermal degradation product (m/z 530), also found in expired formulations.
• Demonstrated cytotoxic effects of thermal degradation products on mononuclear cells.

Conclusions:

• Understanding pharmaceutical degradation pathways is crucial.
• DOX degradation products, especially from thermal decomposition, exhibit toxicity.
• Assessing environmental and human health impacts of pharmaceutical degradation products is essential.