A fast DLLME-LC-MS/MS method for risperidone and its metabolite 9-hydroxyrisperidone determination in plasma samples for therapeutic drug monitoring of patients

Risperidone is an antipsychotic drug commonly used in the treatment of schizophrenia and other psychiatric illnesses. Its main metabolite, 9-hydroxyrisperidone, also called paliperidone, exhibits pharmacological activity similar to risperidone, and the active fraction is the sum of the therapeutic concentrations of both. In this study, a novel method combining dispersive liquid-liquid microextraction and liquid chromatography coupled to mass spectrometry was developed to quantify the active fraction of these antipsychotic drugs in human plasma samples. The chromatographic analysis was performed employing an Ascentis (R) Express C18 chromatographic column (100 x 4.6 mm x 2.7 mu m) and ammonium acetate (10 mmol/L): acetonitrile in gradient elution was employed as mobile phase. The flow rate was 0.5 mL/min, and the total run time was 8 min. The best micro-extraction conditions were chlorobenzene (80 mu L) and acetone (500 mu L) as extractor and dispersing solvent, respectively. The sample pH was adjusted to 12.0 and 10% NaCl was added in the samples in order to increase the ionic strength. The method was completely validated according to Guideline on Bioanalytical Method Validation. Finally, therapeutic drug monitoring capability of the new bioanalytical method was confirmed with the analysis of schizophrenic patient plasma.