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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.
- Source :
-
Clinica Chimica Acta . Feb2022, Vol. 527, p1-10. 10p. - Publication Year :
- 2022
-
Abstract
- • A straightforward LC-MS/MS assay was developed to detect 5 EGFR-TKIs and metabolites. • Semi-quantitative analysis of OSI-413 was performed using OSI-420 calibration. • Systematic evaluation were validated to access the method according to the guidelines. • This method was suitable for routine TDM of EGFR-TKIs in clinical laboratory. • Incurred sample reanalysis indicated the satisfying reproducibility of the method. 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). Afatinib-d 6 , erlotinib-d 6 , OSI-420-d 4, gefitinib-d 6 and osimertinib-C 13 ,d 3 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 C 18 column using a linear gradient elution. LC-MS/MS was conducted in positive ionization mode with multiple reaction monitoring. 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. 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00098981
- Volume :
- 527
- Database :
- Academic Search Index
- Journal :
- Clinica Chimica Acta
- Publication Type :
- Academic Journal
- Accession number :
- 155102277
- Full Text :
- https://doi.org/10.1016/j.cca.2021.12.028