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
- Clin Chim Acta. 2022 Feb 15;527:1-10. doi: 10.1016/j.cca.2021.12.028.
- 1. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University, Beijing, 100191, China.
- 2. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; School of Basic Medical and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China.
- 3. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
- 4. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China.
- 5. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China. Electronic address: [email protected].
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.