A method based on microwave-assisted extraction combined with liquid chromatography-tandem mass spectrometry(MAE/LC-MS/MS) was established for the simultaneous determination of 14 antipsychotic and sedative substances in human nails.About 20 mg of decontaminated and pulverized nail samples was microwave-assistedly extracted for twice in the presence of clozapine-d4 used as the internal standard, and the supernatant was determined by LC-MS/MS using the Allure PFPP column with a mobile phase of methanol(containing 20mmol/L ammonium acetate)-20mmol/L ammonium acetate buffer. Multiple reaction monitoring(MRM) mode was used to analyze 14 antipsychotic and sedative substances. Good linearities(r2≥0.990) over the corresponding range were obtained for all the analytes.The limits of detection(LOD) were in the range of 0.1-50pg/mg and the limits of quantitation(LOQ) were 100pg/mg for most of the analytes.The deviations of intra- and inter-RSD were not more than 7.8%.Accuracies were within ±10.16%.Positive results were obtained from 7 authentic nail samples,which were in good accordance with the drug administration of the corresponding antipsychotic and sedative substances.The developed method presents a simplified,efficient and rapid procedure for sample preparation,and shows high sensitivity and selectivity,which is suitable for the simultaneous analysis of 14 antipsychotic and sedative substances at pg/mg levels in nail samples.