Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring  

作　　者：Lan Chen Yuan Zhang Yi-Xin Zhang Wei-Lai Wang De-Mei Sun Peng-Yun Li Xue-Song Feng Yue Tan 

机构地区：[1]School of Pharmacy,China Medical University,Shenyang,110122,China [2]Institute of Pharmacology and Toxicology Institution,National Engineering Research Center for Strategic Drugs,Beijing,100850,China [3]Department of Gastroenterology,Shengjing Hospital of China Medical University,Shenyang,110022,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第4期439-459,共21页药物分析学报（英文版）

基　　金：supported by the Natural Science Foundation of Liaoning Province,China(Grant No.:2023-MS-172).

摘　　要：Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

关 键 词：TKIs Microextraction technique HRMS methods Pharmacokinetic studies Therapeutic drug monitoring 

分 类 号：R969.1[医药卫生—药理学]