A simple and rapid analytical method is developed and validated for the determination of antiepileptic and antipsychotic drugs in human whole blood using a solid-phase extraction and quantification by gas chromatography-mass spectrometry (GC/MS). Prazepam was used as internal standard (IS). The specificity, linearity, intra-and inter-assay precision and accuracy, and extraction recovery were fully evaluated. The limits of detection and quantification were in the range of 0.52 -0.98 mg/mL and 1.56 -2.97 mg/mL for antiepileptic drugs (pentobarbital, phenobarbital and carbamazepine) and 1.31 -2.94 ng/mL and 3.98 -8.89 ng/mL for antipsychotic drugs (chlorpromazine and thioridazine), respectively. The relative standard deviation (RSD) was less than 7.07%, while the intra-day accuracy was < 3.21% and the inter-day was < 8.80%, referred to RSD. The developed methodology was applied in forensic cases of death caused by phenothiazines in the North of Chile during 2010-2012.