Rapid characterization of thermally stable chemical compounds in solid or liquid states is achieved through thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS). A feature of this technique is that sampling, desorption, ionization, and mass spectrometric detection are four separate events with respect to time and location. A metal probe was used to sample analytes in their solid or liquid states. The probe was then inserted in a preheated oven to thermally desorb the analytes on the probe. The desorbed analytes were carried by a nitrogen gas stream into an ESI plume, where analyte ions were formed via interactions with charged solvent species generated in the ESI plume. The analyte ions were subsequently detected by a mass analyzer attached to the TD-ESI source. Quantification of acetaminophen in aqueous solutions using TD-ESI/MS was also performed in which a linear response for acetaminophen was obtained between 25 and 500 ppb (R(2) = 0.9978). The standard deviation for a reproducibility test for ten liquid samples was 9.6%. Since sample preparation for TD-ESI/MS is unnecessary, a typical analysis can be completed in less than 10 s. Analytes such as the active ingredients in over-the-counter drugs were rapidly characterized regardless of the different physical properties of said drugs, which included liquid eye drops, viscous cold syrup solution, ointment cream, and a drug tablet. This approach was also used to detect trace chemical compounds in illicit drugs and explosives, in which samples were obtained from the surfaces of a cell phone, piece of luggage made from hard plastic, business card, and wooden desk.