Wang Dong, Li Mengrong, Dai Tingting, Zhang Xiangyu, Chen Di
Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Huanhu West Road, Tianjin, China; Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Airport East 5th Road, Tianjin, China.
Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Airport East 5th Road, Tianjin, China.
J Chromatogr A. 2025 Oct 11;1760:466315. doi: 10.1016/j.chroma.2025.466315. Epub 2025 Aug 23.
Accurate quantification of tyrosine kinase inhibitors (TKIs) in plasma is essential for therapeutic drug monitoring (TDM). This study presents a novel solid phase extraction (SPE) method employing hydrophobic polypropylene fabric (PPF)-a fibrous material derived from oil-absorbent pads-as the sorbent. The PPF-SPE device was prepared by directly packing fluffed PPF into syringe barrels, eliminating the need for sieve plates and simplifying column assembly. Integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS), the method enabled sensitive determination of eight clinically relevant TKIs (afatinib, alectinib, ceritinib, dasatinib, sunitinib, pazopanib, tamoxifen, and ibrutinib) in plasma. Key parameters, including PPF amount, sample pH, and desorption conditions, were systematically optimized, yielding high extraction recoveries (83.1-96.4 %) and good reproducibility (RSDs<5.5 %). The method showed excellent linearity (R²>0.99), low detection limits (0.017-0.055 ng/mL), and high intra-/inter-day recoveries (85.1 %-102.6 %) and precision (RSDs<5.3 %). Its practical applicability was validated in spiked plasma under a single-blind design, yielding relative errors of -8.2 % to 5.4 %. Compared to traditional SPE methods, PPF-SPE offers significant advantages in operational simplicity, cost-effectiveness, high throughput, and environmental sustainability.
准确测定血浆中的酪氨酸激酶抑制剂（TKIs）对于治疗药物监测（TDM）至关重要。本研究提出了一种新型固相萃取（SPE）方法，该方法采用疏水性聚丙烯织物（PPF）——一种源自吸油垫的纤维材料——作为吸附剂。PPF-SPE装置是通过将蓬松的PPF直接填充到注射器筒中制备而成，无需筛板，简化了柱组装过程。该方法与液相色谱-串联质谱（LC-MS/MS）联用，能够灵敏地测定血浆中8种临床相关的TKIs（阿法替尼、阿来替尼、色瑞替尼、达沙替尼、舒尼替尼、帕唑帕尼、他莫昔芬和伊布替尼）。对包括PPF用量、样品pH值和解吸条件在内的关键参数进行了系统优化，获得了较高的萃取回收率（83.1-96.4%）和良好的重现性（相对标准偏差<5.5%）。该方法具有出色的线性（R²>0.99）、低检测限（0.017-0.055 ng/mL）以及高日内/日间回收率（85.1%-102.6%）和精密度（相对标准偏差<5.3%）。其实际适用性在单盲设计的加标血浆中得到验证，相对误差为-8.2%至5.4%。与传统SPE方法相比，PPF-SPE在操作简便性、成本效益、高通量和环境可持续性方面具有显著优势。
