Bioactivation and reactivity research advances - 2022 year in review‡

Area of Science:

• Pharmacology
• Toxicology
• Biochemistry

Background:

• The field of drug metabolism and bioactivation has seen significant advancements over the last 50 years.
• Technological progress in hardware, software, machine learning (ML), and artificial intelligence (AI) has been a major driver of this progress.
• The journal *Drug Metabolism and Disposition* celebrates its 50th anniversary, highlighting the field's evolution.

Purpose of the Study:

• To review the exponential advancements in drug metabolism and bioactivation technologies.
• To highlight the impact of integrated technological approaches on understanding drug bioactivation pathways and toxicity.
• To emphasize the role of these advancements in developing novel therapeutics for unmet medical needs.

Main Methods:

• Evolution of Liquid Chromatography-Mass Spectrometry (LC-MS) platforms.
• Improvements in automation for enhanced accuracy, precision, and throughput of assays.
• Advancements in sample generation and processing using diverse reagents and bio-matrices.
• Application of *in silico* platforms, including ML and AI, alongside traditional methods.

Main Results:

• Continued evolution of LC-MS platforms supports key applications in drug metabolism.
• Automation is enhancing the efficiency and reliability of supporting assays.
• *In silico* tools, combined with traditional methods, are significantly improving the understanding of bioactivation pathways and their role in toxicity.

Conclusions:

• Technological integration, including AI and ML, is crucial for advancing drug metabolism and bioactivation research.
• Enhanced understanding of bioactivation pathways contributes to predicting and mitigating drug toxicity.
• These collective advancements facilitate the development of improved medicines for patients with critical or unmet needs.