Determining plasma and cerebrospinal fluid concentrations of EGFR-TKI in lung cancer patients

Area of Science:

• Pharmacology
• Analytical Chemistry
• Oncology

Background:

• Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are crucial for advanced non-small cell lung cancer (NSCLC).
• Accurate measurement of EGFR-TKI concentrations in plasma and cerebrospinal fluid (CSF) is essential for effective therapeutic drug monitoring.
• Current methods may lack the speed and reliability needed for routine clinical application.

Purpose of the Study:

• To develop and validate a rapid and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method.
• To quantify gefitinib, erlotinib, afatinib, and osimertinib concentrations in plasma and CSF.
• To assess the CSF penetration of these EGFR-TKIs in NSCLC patients.

Main Methods:

• Developed a UHPLC-MS/MS assay utilizing multiple reaction monitoring (MRM) for quantification.
• Employed protein precipitation for sample preparation to remove interfering substances.
• Validated the assay for linearity, precision, and accuracy according to established guidelines.

Main Results:

• The method demonstrated satisfactory linearity, precision, and accuracy.
• Successfully measured EGFR-TKI concentrations in plasma (n=44) and CSF (n=6) from NSCLC patients.
• Determined median plasma concentrations and calculated CSF penetration rates for erlotinib, afatinib, and osimertinib.

Conclusions:

• The validated UHPLC-MS/MS assay provides a rapid and reliable tool for therapeutic drug monitoring of EGFR-TKIs.
• This method facilitates personalized treatment strategies by predicting EGFR-TKI effectiveness and toxicity in NSCLC patients.
• The findings support the advancement of precision medicine in lung cancer care.