Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported i n the literature. This article describes the case of a 25-year-old man foun d dead at home who had been prescribed olanzapine for schizophrenia. This c ase is unique because of the measurement of olanzapine in brain tissue obta ined from seven regions in addition to the commonly collected biologic matr ices. Olanzapine was detected and quantitated by basic liquid-liquid extrac tion followed by dual-column gas chromatographic analysis with nitrogen pho sphorus detection. The assay had a limit of detection of 0.05 mg/L and an u pper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionizati on. The concentrations of olanzapine measured in this case were as follows (mg or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric content s). In the brain, the following distribution of olanzapine was determined ( mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (a mygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (rig ht frontal cortex). The cause of death was determined to be acute intoxicat ion by olanzapine, and the manner of death was accidental.