Simultaneous determination of osimertinib and almonertinib concentrations in human plasma and cerebrospinal fluid using UPLC-MS/MS method and its clinical applications
- 1Department of Pharmacy, The Fourth Hospital of Hebei Medical University
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.
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BibTeX
@article{yin2026simultaneous,
title = {{Simultaneous determination of osimertinib and almonertinib concentrations in human plasma and cerebrospinal fluid using UPLC-MS/MS method and its clinical applications}},
author = {Jintuo Yin and Yalan Zuo and Xin Wang and Zhentao Zhang and Hongyu Yue and Jian Shi and Ying Han and Jiang Liu and Ping Liang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1943759},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1943759/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Simultaneous determination of osimertinib and almonertinib concentrations in human plasma and cerebrospinal fluid using UPLC-MS/MS method and its clinical applications
AU - Jintuo Yin
AU - Yalan Zuo
AU - Xin Wang
AU - Zhentao Zhang
AU - Hongyu Yue
AU - Jian Shi
AU - Ying Han
AU - Jiang Liu
AU - Ping Liang
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1943759
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1943759/full
AB - 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.
SN - 1663-9812
ER -