Screening and quantification of antipsychotic drugs in human brain tissue by liquid chromatography-tandem mass spectrometry: application to postmortem diagnostics of forensic interest

A quantitative LC-MS/MS method has been developed for the simultaneous determination of 17 antipsychotic drugs in human postmortem brain tissue. Sample preparation was performed using Hybrid Solid Phase Extraction-Precipitation technology for the removal of endogenous protein and phospholipid interferences. The chromatographic separation was performed for 16 min on a C8 column, which used a gradient elution of formate ammonium and acetonitrile, and a flow rate gradient. Triple quadrupole mass spectrometry was employed to generate tandem mass spectrometric (MS/MS) data of the target analytes to select the ion m/z signals. Quantitation of the analytes was performed by operating in the dynamic multiple reaction monitoring (dMRM) mode using an electrospray ionization interface. Calibration curves prepared in the spiked brain tissue were linear in the range 20-8000 ng/g (r(2)>0.993) for all drugs (except olanzapine). Within- and between-day coefficients of variation were lower than 25% for all drugs at the LOQ. The LOQ in the matrix ranged between 2 ng/g and 80 ng/g. The method was successfully applied to the unequivocal identification and accurate quantification of antipsychotic drugs in human postmortem brain tissues: therefore, this method can be used in forensic investigations.