Work

Simultaneous determination of osimertinib and almonertinib concentrations in human plasma and cerebrospinal fluid using UPLC-MS/MS method and its clinical applications

Year: 2026

Type: article

Abstract: Objectives: This study aimed to establish a sensitive analytical method to simultaneously measure concentrations of two third-generation EGFR inhibitors, osimertinib and almonertinib, in human plasma and cerebrospinal fluid. A further objective was to investigate the relationship between these drug concentrations, their penetration into the central nervous system, and clinical treatment efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. Methods: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and fully validated for the simultaneous quantification of osimertinib and almonertinib. Plasma and cerebrospinal fluid samples were collected from twenty NSCLC patients with brain metastases (7 receiving osimertinib, 13 receiving almonertinib) at steady-state trough concentration. Drug concentrations were measured, and blood-brain barrier penetration rates were calculated (cerebrospinal fluid/plasma concentration ratio × 100%). Treatment efficacy was assessed via lung CT and brain MRI using RECIST criteria. Results: The validated UPLC-MS/MS method demonstrated excellent sensitivity, specificity, and accuracy for both drugs in both matrices. Significant inter-individual variability was observed in plasma concentrations, cerebrospinal fluid concentrations, and penetration rates. For both drugs, steady-state plasma concentration showed no significant correlation with lung tumor response. However, higher cerebrospinal fluid concentration and penetration rate were positively correlated with improved treatment efficacy for brain metastases, as evidenced by better outcomes on brain MRI. Conclusion: Therapeutic drug monitoring of osimertinib and almonertinib in cerebrospinal fluid, rather than plasma alone, may provide a more relevant indicator for assessing and optimizing treatment efficacy against brain metastases in NSCLC. This study would develop personalized treatment plans for NSCLC patients with brain metastases, providing important evidence for clinical practice.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1943759