https://scholars.lib.ntu.edu.tw/handle/123456789/630367
標題: | Determining plasma and cerebrospinal fluid concentrations of EGFR-TKI in lung cancer patients | 作者: | GUAN-YUAN CHEN SHENG-KAI LIANG Wei, Yu-Feng TE-I WENG KUAN-YU CHEN |
關鍵字: | EGFR-TKI; LC‒MS/MS; Lung cancer; Precision medicine; Therapeutic drug monitoring | 公開日期: | 15-五月-2023 | 卷: | 669 | 來源出版物: | Analytical biochemistry | 摘要: | Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used to treat advanced non-small cell lung cancer (NSCLC). A rapid and reliable method for measuring plasma and cerebrospinal fluid (CSF) concentrations of EGFR-TKIs is needed for therapeutic drug monitoring. By using UHPLC‒MS/MS with multiple reaction monitoring mode, we developed a method for rapidly determining the plasma and CSF concentrations of gefitinib, erlotinib, afatinib, and osimertinib. Protein precipitation was employed to remove protein interference for plasma and CSF matrix. The LC‒MS/MS assay was validated to be satisfactory in terms of linearity, precision, and accuracy. This method was successfully applied to measure plasma (n = 44) and CSF (n = 6) concentrations of EGFR-TKIs in NSCLC patients. The chromatographic separation was achieved by a Hypersil Gold aQ column within 3 min. The median plasma concentrations were 325.76, 1981.50, 42.62, 40.27, and 340.92 ng/ml for gefitinib erlotinib, afatinib 30 mg/day, afatinib 40 mg/day, and osimertinib, respectively. The CSF penetration rates were 2.15% for the patients receiving erlotinib therapy, 0.59% for afatinib, 0.08-1.12% for osimertinib 80 mg/day, and 2.18% for those receiving osimertinib 160 mg/day. This assay helps to predict the effectiveness and toxicities of EGFR-TKIs in the pursuit of precision medicine for lung cancer patients. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630367 | ISSN: | 00032697 | DOI: | 10.1016/j.ab.2023.115115 |
顯示於: | 醫學系 |
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