Rapid and Sensitive Quantification of Osimertinib in Human Plasma Using a Fully Validated MALDI-IM-MS/MS Assay

Area of Science:

• Oncology
• Pharmacology
• Analytical Chemistry

Background:

• Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is crucial for treating EGFR-mutated non-small cell lung cancer, including resistant cases.
• Its use as a first-line therapy expands its application in lung oncology.
• Personalized medicine necessitates monitoring patient drug concentrations and emerging resistance to optimize osimertinib treatment.

Purpose of the Study:

• To develop and validate a rapid and sensitive quantification method for osimertinib in plasma.
• To propose matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) as an alternative to traditional LC-MS/MS methods.
• To facilitate efficient therapeutic drug monitoring for personalized osimertinib therapy.

Main Methods:

• Quantification of osimertinib in human plasma using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
• Assay development focused on rapid sample preparation, analysis, and data extraction.
• Method validation according to US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines.

Main Results:

• A novel MALDI-MS assay for osimertinib quantification was successfully developed.
• The assay demonstrated rapid analysis with a turnaround time of less than 3 hours per sample.
• A lower limit of quantification (LLOQ) of 5 ng/mL in plasma was achieved.
• The method was fully validated for bioanalytical accuracy and sensitivity.

Conclusions:

• MALDI-MS provides a time-efficient alternative to LC-MS/MS for quantifying osimertinib in plasma.
• This method supports personalized medicine by enabling effective therapeutic drug monitoring.
• The developed assay is crucial for optimizing targeted therapies and managing treatment resistance in lung cancer patients.