舒尼替尼、N-去甲基伊马替尼、达沙替尼、伊马替尼和博舒替尼是酪氨酸激酶抑制剂 (TKI)，常用于治疗多种癌症。然而，不适当的 TKI 浓度可能会导致治疗无效或出现多种不良反应。因此，开发快速、灵敏的 TKI 分析方法对于安全用药至关重要。在这项工作中，构建了固相微萃取（SPME）探针与电喷雾电离质谱（ESI-MS）耦合平台相结合，用于快速、灵敏地测定TKI。共价有机框架（COF）涂覆的固相微萃取探针由2,4,6-三（4-氨基苯基）-1,3,5-三嗪（TAPT）和2,5-二丁氧基对苯二甲醛（DBTA）通过原位层制成逐层化学键合合成策略。 TAPT-DBTA-SPME 探针表现出多种有利的特性，使其适合 TKI 的富集。在最佳条件下，所开发的分析方法显示出 TKI 的宽线性范围 (0.05-500.00 µg/L)、低检测限 (0.02 µg/L) 和高富集因子 (51-203)。所开发的分析方法已成功应用于小鼠血浆和组织基质中 TKI 的药代动力学研究，表明所提出的分析方法有望用于临床应用和代谢监测。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Sunitinib, N-desmethyl imatinib, dasatinib, imatinib, and bosutinib are tyrosine kinase inhibitors (TKIs) that are commonly employed in the treatment of a multitude of cancers. However, the inappropriate concentrations of TKIs can result in ineffective treatment or the emergence of multiple adverse effects. Consequently, the development of a rapid and sensitive analytical method for TKIs is of paramount importance for the safe administration of drugs. In this work, solid-phase microextraction (SPME) probe combined with an electrospray ionization mass spectrometry (ESI-MS) coupling platform was constructed for rapid and sensitive determination of TKIs. The covalent organic frameworks (COFs) coated SPME probe was made of 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and 2,5-dibutoxyterephthalaldehyde (DBTA) by in-situ layer-by-layer chemical bonding synthesis strategy. The TAPT-DBTA-SPME probe exhibited several advantageous properties which rendered it suitable for the enrichment of TKIs. Under the optimal conditions, the developed analytical method demonstrated a broad linear range (0.05-500.00 µg/L), a low limit of detection (0.02 µg/L) and a high enrichment factor (51-203) for TKIs. The developed analytical method was successfully applied to a pharmacokinetic study of TKIs in mouse plasma and tissue matrix, demonstrating that the proposed analytical method has promise for clinical applications and metabolic monitoring.Copyright © 2024 Elsevier B.V. All rights reserved.