In order to discover new matrices suitable for the analyses of low molecular-weight compounds using positive-ion mode matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (MS), 5-(3-trifluoromethylbenzylidene)thiazolidine-2,4-dione (3-CF3-BTD) was synthesized, and its effectiveness was compared with that when commercially available α-cyano-4-hydroxycinnamic acid was used. 3-CF3-BTD was sufficiently sensitive to analyze neurotransmitters, i.e., dopamine, serotonin, histamine, and epinephrine, in amounts of several picomoles. Similar to vacuum MALDI experiments, atmospheric-pressure MALDI-MS measurements using 3-CF3-BTD as a matrix also detected dopamine.