On-site therapeutic drug analysis with paper-capillary spray ionization and miniature mass spectrometry system

Therapeutic drug monitoring ensures safe and effective pharmacotherapy by maintaining drug concentrations within a therapeutic range. However, conventional liquid chromatography-mass spectrometry workflows are restricted to clinical laboratories and limited by complicated sample preparation and long analysis times. Here we describe an on-site therapeutic drug monitoring protocol by integrating paper-capillary spray ionization with a miniature linear ion trap mass spectrometer. It consumes several microliters of biofluid without sample preparation and can provide results in 2 min. The protocol was validated by analyzing linezolid, carbamazepine, imatinib, and lamotrigine in blood samples, showing low limits detection as low as 50 ng/mL, RSD below 15%, and good linearity (R² > 0.99) across five orders of magnitude. The protocol is promising in fast and on-site monitoring of a wide range of therapeutic drugs in biofluids.