A simple and sensitive analytical method for determining residues of the tranquilizer chlorpromazine in foods such as livestock products, seafood, and honey was developed. The method involves solvent extraction with acetone, clean-up using InertSep MC-1 strong cation-exchange solid-phase extraction cartridges, and liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis with selective reaction monitoring in positive ionization mode. Because chlorpromazine was gradually degraded in the extraction step when using methanol or ethanol as the extraction solvent, we examined the stability of chlorpromazine in the presence of various solvents. Acetone was selected as the extraction solvent because chlorpromazine was not degraded over time in acetone extracts. Because chlorpromazine adsorbs onto glass surfaces, polypropylene tubes were used for the extraction step to prevent loss of the recovery. The developed method was validated using eight food products spiked with chlorpromazine at 0.1 μg/ kg. The validation results exhibited excellent recovery (range, 86-106%) and precision (variation < 10%). The limit of quantification (S/N ≥ 10) of the developed method was 0.1 μg/kg. The proposed method would be very useful for regulatory monitoring of the illegal use of chlorpromazine in foods.