Critical review of recent advances in sample pretreatment and determination methods for therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) is an important bridge connecting drugs, patients, and therapeutic effects. It transcends a purely technical role, representing a patient-centered methodology grounded in data, with the ultimate goal of optimizing treatment outcomes. Therefore, it is necessary to have a good understanding of the pretreatment methods and analysis techniques used in TDM. Pretreatment methods include traditional methods such as protein precipitation and liquid-liquid extraction, as well as new methods such as liquid phase microextraction, magnetic solid phase extraction, solid phase microextraction, and QuEChERS. Adding some new materials, such as molecularly imprinted polymers, metal-organic frameworks, and reagents like deep eutectic solvents, is a big step forward in pretreatment technology. Analytical techniques include liquid/gas chromatography-tandem mass spectrometry, sensors, capillary electrophoresis, and spectroscopic methods. At present, the main research direction is to apply high-resolution mass spectrometry and to use advanced materials in sensor technology. This review provides a critical evaluation of the strengths and limitations of existing methods and identifies future directions for development.