In animal husbandry, diazepam, chlorpromazine, and promethazine are illegally used to promote growth and increase weight, thus leading to food safety problems. Here, an easy and sensitive method was developed for simultaneous determination of these three drugs in lamb liver. Liver sample was extracted with 25 % ammonium hydroxide–ethyl acetate–chloroform (2:17:2, v/v/v) and cleaned up with an alumina N cartridge. The target compounds were quantified and identified by ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization tandem mass spectrometry (ESI/MS/MS) operated in multiple reaction monitoring mode. At the fortified levels of 0.5–5 μg kg−1, recoveries of all drugs in lamb liver were between 94.84 ± 9.78 % to 99.52 ± 11.25 % with 4.48–11.27 % of intra-day coefficient variations (CVs) and 5.72–12.00 % of inter-day CVs. Limit of detection and limit of quantification of the three drugs were 0.05–0.16 μg kg−1 and 0.15–0.50 μg · kg−1, respectively. The method was demonstrated to be reliable and sensitive.