首页|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
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
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NSTL
Elsevier
? 2021Background 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.
EGFR-TKIsLC–MS/MSMetabolitesNon-small cell Lung cancerTherapeutic drug monitoring
Xiong X.、Zhang Y.、Wang Z.、Zhou C.、Yang P.、Du X.、Yang L.、Liu W.
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Department of Pharmacy Peking University Third Hospital
NSTL
Elsevier
