Multi-analyte LC-MS/MS quantification of 38 antipsychotics and metabolites in plasma: Method validation & application to routine analyses

•Simultaneous quantitative analysis of 38 antipsychotics or metabolites.•Simple and fast sample preparation/chromatography.•Easy to combine with previously published methods for psychoactive substances.•Applicable in therapeutic drug monitoring, clinical samples and forensic case work. The past decades have seen a rise in the prescription of antipsychotic drugs in the European population, despite the risk of extra-pyramidal, metabolic and cardiac side effects. A multi-analyte liquid chromatography – triple quadrupole mass spectrometry method was developed for the quantification of 38 antipsychotic drugs in plasma. Samples were extracted by a straightforward liquid–liquid extraction with methyl-tertiary-butyl-ether and the compounds of interest were chromatographically separated within 6 min. Calibration curves covered the recommended therapeutic range for all compounds, in addition to sub- and supratherapeutic concentrations for most. The method was successfully validated according to the European Medicines Agency guidelines on bioanalytical method validation. Analysis of medico-legal samples confirmed the relatively common use of the second generation antipsychotics quetiapine and olanzapine, as well as the continued presence of the first generation antipsychotic haloperidol.