Simultaneous Determination of Fourteen Antipsychotic Drugs in Whole Blood by Solid Phase Extraction and Liquid Chromatography Tandem Mass Spectrometry

Anti-psychotic drugs are commonly prescribed to patients to treat several mental conditions, such as bipolar, schizophrenia, and manic-depressive disorder. The analysis of anti-psychotic drugs in blood is a common practice in clinical and forensic toxicology, to monitor drug treatment (therapeutic drug monitoring) or to explain the cause of the impairment or intoxication in human performance and in postmortem cases. However, most of the current studies have been performed in plasma, and a limited number in blood. We developed and validated a method to confirm and quantify a panel of commonly prescribed anti-psychotic drugs in whole blood using solid phase extraction (SPE) and liquid chromatography tandem mass spectrometry (LC-MSMS). The anti-psychotic drugs in the panel were: aripiprazole, asenapine, clozapine, olanzapine, 9-hydroxyrisperdone (paliperidone), quetiapine, chlorpromazine, fluphenazine, perphenazine, risperidone, haloperidol, lurasidone, ziprasidone, and brexpiprazole. The blood samples were extracted by solid phase extraction using cation exchange cartridges. The chromatographic separation was performed in reversed-phase column using 0.1% formic acid in water and methanol for mobile phases, and in the mass spectrometer two MRM (multiple reaction monitoring) transitions were acquired in positive electrospray mode. The method was validated showing good linearity with a range of 1 to 1000ng/mL. Limit of quantification was established at 1ng/mL and the drug panel was shown to be both accurate and precise. Other validation studies completed were dilution, carryover, selectivity, specificity and stability. When an authentic donor was used to test the method, 9-hydroxyrisperidone was detected and quantitated. The method validation of this panel of psychotropic medications is a step in a larger project that assesses the steady state levels of therapeutic dosages