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

Guan-Yuan Chen; Sheng-Kai Liang; Yu-Feng Wei; Te-I Weng; Kuan-Yu Chen

doi:10.1016/j.ab.2023.115115

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

Anal Biochem. 2023 May 15:669:115115. doi: 10.1016/j.ab.2023.115115. Epub 2023 Mar 15.

Authors

Guan-Yuan Chen¹, Sheng-Kai Liang², Yu-Feng Wei³, Te-I Weng⁴, Kuan-Yu Chen⁵

Affiliations

¹ Forensic and Clinical Toxicology Center, National Taiwan University Hospital, Taipei, Taiwan; Department and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan; Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan.
³ School of Medicine for International Students, College of Medicine, and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan.
⁴ Forensic and Clinical Toxicology Center, National Taiwan University Hospital, Taipei, Taiwan; Department and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: tuff.chen@msa.hinet.net.

PMID: 36931580
DOI: 10.1016/j.ab.2023.115115

Abstract

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used to treat advanced non-small cell lung cancer (NSCLC). A rapid and reliable method for measuring plasma and cerebrospinal fluid (CSF) concentrations of EGFR-TKIs is needed for therapeutic drug monitoring. By using UHPLC‒MS/MS with multiple reaction monitoring mode, we developed a method for rapidly determining the plasma and CSF concentrations of gefitinib, erlotinib, afatinib, and osimertinib. Protein precipitation was employed to remove protein interference for plasma and CSF matrix. The LC‒MS/MS assay was validated to be satisfactory in terms of linearity, precision, and accuracy. This method was successfully applied to measure plasma (n = 44) and CSF (n = 6) concentrations of EGFR-TKIs in NSCLC patients. The chromatographic separation was achieved by a Hypersil Gold aQ column within 3 min. The median plasma concentrations were 325.76, 1981.50, 42.62, 40.27, and 340.92 ng/ml for gefitinib erlotinib, afatinib 30 mg/day, afatinib 40 mg/day, and osimertinib, respectively. The CSF penetration rates were 2.15% for the patients receiving erlotinib therapy, 0.59% for afatinib, 0.08-1.12% for osimertinib 80 mg/day, and 2.18% for those receiving osimertinib 160 mg/day. This assay helps to predict the effectiveness and toxicities of EGFR-TKIs in the pursuit of precision medicine for lung cancer patients.

Keywords: EGFR-TKI; LC‒MS/MS; Lung cancer; Precision medicine; Therapeutic drug monitoring.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Afatinib / therapeutic use
Carcinoma, Non-Small-Cell Lung* / drug therapy
Chromatography, Liquid
ErbB Receptors / genetics
Erlotinib Hydrochloride / therapeutic use
Gefitinib / therapeutic use
Humans
Lung Neoplasms* / drug therapy
Mutation
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Tandem Mass Spectrometry

Substances

osimertinib
Afatinib
Erlotinib Hydrochloride
Gefitinib
Protein Kinase Inhibitors
ErbB Receptors
EGFR protein, human