LC–MS/MS in Therapeutic Drug Monitoring (TDM): Advances and Clinical Applications

Therapeutic Drug Monitoring (TDM) is a cornerstone of individualized pharmacotherapy, aiming to optimize drug efficacy while minimizing toxicity through precise measurement of drug concentrations in biological matrices. Over the past two decades, liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) has emerged as the gold-standard analytical platform for TDM, superseding conventional immunoassays by virtue of its superior sensitivity, specificity, and multiplexing capabilities. This review article comprehensively examines the fundamental principles of LC–MS/MS as applied to TDM, recent technological advances including microsampling strategies, automation, and high-resolution mass spectrometry, as well as the growing body of clinical evidence supporting its implementation across key drug classes—immunosuppressants, antimicrobials, antiepileptics, psychotropic agents, and targeted anticancer drugs. Current challenges, regulatory considerations, and future prospects in the integration of LC–MS/MS with pharmacokinetic modelling and artificial intelligence are also discussed.