A new analytical method using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was developed for screening and confirmation of 10 unapproved sedative drugs in feeds. The samples were extracted using the solution of methanol-0.1 mol/L HCl (9:1, v/v), and the extracts were centrifuged and then directly purified through MCX cartridges. The identification and detection were achieved in positive electrospray ionization (ESI) mode using Q-TOF-MS. The potential of UPLC-Q-TOF MS for confirmatory analysis was shown by determining the accurate mass of all the compounds and fragment ions upon collision-induced-dissociation (CID) at different energies. The extra mass measurement errors for all the sedative drugs were found to be within 5 ppm. The calibration graphs were linear in the concentration range of 5-100 microg/L with the correlation coefficients more than 0.99 for the 10 drugs. The limits of quantification (LOQ, S/N = 10) were 8 microg/kg for nitrazepam, zolpidem and thioridazine; 10 microg/kg for thriazolam, estazolam, diazepam, promethazine, chlorpromazine and midazolam; 20 microg/kg for clozapine. The recoveries for all the compounds in feeds were 60.6%-108.5% with the relative standard deviations less than 10% at the spiked levels of LOQ, 2LOQ and 4LOQ.