Simultaneous Quantification of 38 Psychotropic Drugs and Relevant Metabolites in Blood using LC-MS-MS

The trend for the concomitant prescription of antidepressants and antipsychotics is increasing. This calls for a veracious screening and quantifying method for forensic and clinical use. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the simultaneous determination and quantification of 38 antidepressants, antipsychotics and relevant metabolites in small volumes (200 μL) of human whole blood. Analytes and deuterated internal standards were extracted using liquid-liquid extraction. The separation, determination and quantification of the analytes were performed using an LC-MS-MS system equipped with an ACQUITY UPLC® BEH Phenyl Column under a positive electrospray ionization mode. After validation, the analytical procedure was proved to be highly sensitive, with a limit of detection ranging from 0.0005 to 1 ng/mL and a lower limit of quantification ranging from 0.002 to 2 ng/mL. Bias and within- and between-run precision were within 14.7% for all analytes. Recoveries were reproducible and those of 35 analytes were >50%. Dilution integrity was evaluated to ensure that the therapeutic and toxic blood concentration ranges of target compounds were fully covered. Finally, this method was applied to authentic whole blood samples collected from two forensic cases, which demonstrated its practical usefulness of providing accurate and comprehensive information concerning the previous medication of the deceased.