Simultaneous quantitative detection of afatinib, erlotinib, gefitinib, icotinib, osimertinib and their metabolites in plasma samples of patients with non-small cell lung cancer using liquid chromatography-tandem mass spectrometry.

Abstract

BACKGROUND AND AIMS:

As numerous studies have reported the concentration-exposure relationships of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), therapeutic drug monitoring is a promising approach in lung cancer treatment, aiming to avoid treatment failure or toxicity. A new method for the simultaneous analysis of five EGFR-TKIs (afatinib, erlotinib, gefitinib, icotinib and osimertinib) and their metabolites in human plasma samples was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

MATERIALS AND METHODS:

Afatinib-d6, erlotinib-d6, OSI-420-d4, gefitinib-d6 and osimertinib-C13,d3 were used as internal standards (ISs). The samples were prepared by liquid-liquid extraction using tert-butyl methyl ether. Chromatographic separation was undertaken on an XBridge C18 column using a linear gradient elution. LC-MS/MS was conducted in positive ionization mode with multiple reaction monitoring.

RESULTS:

The proposed method showed satisfactory results in terms of linearity, sensitivity, specificity, precision (intra- and inter-day coefficients of variation ranged from 1.1 to 13.9%), and accuracy (from 93.3 to 111.1%). The IS-normalized matrix factors were below 15%. The sensitivity and linearity were highly appropriate for the expected concentrations according to the analysis of samples from non-small cell lung caner (NSCLC) patients who received EGFR-TKIs.

CONCLUSIONS:

The proposed method showed an acceptable reproducibility, high sensitivity and selectivity, and low matrix effects. This method could be significant for monitoring plasma concentrations of the mentioned EGFR-TKIs in NSCLC patients, aiming to improve the efficacy and safety of targeted therapies.

• Authors: Xin Xiong, Yuanyuan Zhang, Ziyu Wang, Congya Zhou, Ping Yang, Xin Du, Li Yang, Wei Liu
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 527 Pg. 1-10 (Feb 15 2022) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 34999058 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Acrylamides
• Aniline Compounds
• Crown Ethers
• Protein Kinase Inhibitors
• Quinazolines
• osimertinib
• Afatinib
• icotinib
• Erlotinib Hydrochloride
• Gefitinib

Topics

• Acrylamides
• Afatinib
• Aniline Compounds
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Chromatography, Liquid
• Crown Ethers
• Erlotinib Hydrochloride
• Gefitinib
• Humans
• Lung Neoplasms (drug therapy)
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• Quinazolines
• Reproducibility of Results
• Tandem Mass Spectrometry