Objective:

To present a new analytical workflow that eliminates the need for radioactive labeling in drug metabolism studies by using fluorine tracking.

Key Findings:

• The new method achieves detection limits below 1 ng on-column.
• ICP-MS provides a uniform, quantitative response across parent drugs and metabolites without the need for radiolabeled compounds.
• The workflow shows comparable performance to traditional ¹⁴C radioactivity detection in both in vitro and in vivo samples.
• Fluorine is present in up to half of drugs in development and has minimal background in biological matrices.

Interpretation:

The fluorine tracking method allows for sensitive, quantitative metabolite profiling earlier in drug development, enhancing safety by avoiding radioactivity exposure.

Limitations:

• The study does not address potential limitations in the detection of non-fluorinated compounds.
• Further validation may be required for broader applications beyond drug metabolism.

Conclusion:

This innovative method could streamline ADME workflows and expand study design flexibility, with potential applications in environmental analysis of fluorinated compounds.