We aim to develop an efficient and non-invasive strategy for monitoring of drugs and their metabolites via human skin. Probe sampling was combined with thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) to characterize trace terbinafine, which was secreted on patient's skin after ingesting terbinafine tablets. The terbinafine ion signals were directly detected in the samples collected from different skin regions and the signals were monitored for 8 weeks. The detection and location of terbinafine via the skin suggest that the methods are useful in rapidly and noninvasively collecting the molecular information of the ingested drug on skin for pharmacokinetic studies.