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10.1016-j.jchromb.2022.123245 |
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|a 15700232 (ISSN)
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|a Development and validation of a new liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of afatinib, dacomitinib, osimertinib, and the active metabolites of osimertinib in human serum
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|b Elsevier B.V.
|c 2022
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|z View Fulltext in Publisher
|u https://doi.org/10.1016/j.jchromb.2022.123245
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|a Reports on the therapeutic drug monitoring (TDM) of second- and third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer patients are limited and are required to improve the safety of EGFR-TKI therapy. Some EGFR-TKIs have active metabolites with similar or higher potency compared with the parent compounds; thus, monitoring the parent compound as well as its active metabolites is essential for truly effective TDM. In this study, we developed and validated a method that simultaneously quantifies second- and third-generation EGFR-TKIs (afatinib, dacomitinib, and osimertinib) and the active metabolites of osimertinib, AZ5104 and AZ7550, in the human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The clinical application of the method was also evaluated. The analytes were extracted from a 100 μL serum sample using a simple protein precipitation method and analyzed using LC-MS/MS. Excellent linearity of calibration curves was observed at ranges of 2.5–125.0 ng/mL for afatinib, 2.5–125.0 ng/mL for dacomitinib, 4.0–800.0 ng/mL for osimertinib, 1.0–125.0 ng/mL for AZ5104, and 2.5–125.0 ng/mL for AZ7550. The precision and accuracy were below 14.9% and within ± 14.9% of the nominal concentrations, respectively. The mean recovery was higher than 94.7% and the coefficient of variation (CV) was lower than 8.3%. The mean internal-standard normalized matrix factors ranged from 94.6 to 111.9%, and the CVs were lower than 9.7%. This analytical method met the acceptance criteria of the U.S. Food and Drug Administration guidelines. The method was also successfully applied to the analysis of 45 clinical samples; it supports the efficient and valuable analysis for TDM investigations of EGFR-TKIs. © 2022 The Authors
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|a Active metabolites
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|a Amino acids
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|a Biological organs
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|a Biomolecules
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|a Diseases
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|a Drug products
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|a Enzymes
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|a Epidermal growth factor receptors
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|a Epidermal growth factor receptor-tyrosine kinase inhibitor
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|a Epidermal growth factor receptor-tyrosine kinase inhibitors
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|a Human serum
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|a Human serum
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|a Lc.ms/ms
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|a LC-MS/MS
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|a LC-MS-MS
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|a Liquid chromatography
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|a Mass spectrometry
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|a Metabolites
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|a Non small cell lung cancer
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|a Non-small cell lung cancer
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|a Patient monitoring
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|a Patient treatment
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|a Precipitation (chemical)
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|a Protein precipitation
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|a Protein precipitation
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|a Receptor-tyrosine kinase
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|a Safety factor
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|a Tyrosine kinase inhibitor
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|a Chishima, H.
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|a Hakamata, J.
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|a Ikemura, S.
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|a Ishikawa, E.
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|a Jibiki, A.
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|a Kawazoe, H.
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|a Kimura, M.
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|a Kuniyoshi, O.
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|a Muramatsu, H.
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|a Nakada, H.
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|a Nakajima, H.
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|a Nakamura, T.
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|a Nakaya, N.
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|a Sato, I.
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|a Suehiro, N.
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|a Suzuki, S.
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|a Yokoyama, Y.
|e author
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|t Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
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