Abstract: A rapid method for the simultaneous determination of 42 psychoactive drugs and their metabolites (barbitals, benzodiazepines, tricyclic antidepressants, phenothiazines, etc.) in human plasma and urine was developed using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After a simple protein precipitation step, the analysis of the drugs and the metabolites was achieved on an Acquity UPLC BEH C18 column by using the gradient elution with ammonium acetate and methanol-acetonitrile (1:1, v/v) as the mobile phases, and detected by electrospray ionization-tandem mass spectrometry in the multiple reaction monitoring (MRM) mode operated simultaneously in both positive and negative modes by rapid switching, and quantified by matrix-match standard solution. The average recoveries were 60.2%~125% and 64.5%~126% for the drugs in plasma and urine except those of perphenazine, thioridazine and chloropromazine in plasma were 37.6%~57.5%, 36.3%~48.3%, 52.4%~67.4%, respectively; trazodone and diazepam in urine were 100%~142% and 108%~177%, respectively. The relative standard deviations (RSDs) of all the drugs in plasma and urine were within 0.8%~26% and 2.6%~18% (n=6), respectively. The detection limits of the 4 barbitals ranged from 20 to 100 mg/L and those of the other drugs ranged from 0.05 to 2.0 mg/L. The method is simple, selective and sensitive to detect drugs for both clinical and forensic purposes.

Key words: confirmation, plasma, psychoactive drugs, urine , ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)