Therapeutic drug monitoring and advances in key analytical techniques for dihydrofolate reductase inhibitors.

Dihydrofolate reductase (DHFR) inhibitors are a class of drugs that exert their effects by inhibiting the activity of DHFR and interfering with folate metabolism, thereby blocking DNA synthesis. They are widely used in anti-tumor therapy and immunomodulation. Due to their narrow therapeutic window and significant individual variability, excessively high blood concentrations can lead to severe adverse reactions such as bone marrow suppression and hepatorenal toxicity, while low concentrations may compromise efficacy. Therefore, therapeutic drug monitoring (TDM) is essential. In actual biological samples, the target analyte concentrations are typically low, ranging from nanomolar to micromolar levels. Moreover, the sample matrix is complex, containing numerous endogenous interferences as well as potential metabolites and co-administered drugs, posing challenges for accurate quantification. Consequently, it is necessary to conduct timely updates and summaries of sample pretreatment techniques and detection methods to improve sensitivity, selectivity, and analytical efficiency, meeting the demands of precision clinical medication and pharmacokinetic research.