Determination of Olanzapine in a Postmortem Case

• Published in: Journal of analytical toxicology Vol. 22; no. 7; pp. 605 - 609
• Main Authors: Jenkins, Amanda J., Sarconi, Krista M., Raaf, Heather N.
• Format: Journal Article
• Language: English
• Published: Niles, IL Oxford University Press 01.11.1998; Preston
• Subjects: Adult; Antipsychotic Agents - analysis; Antipsychotic Agents - blood; Antipsychotic Agents - cerebrospinal fluid; Antipsychotic Agents - urine; Autopsy; Benzodiazepines; Bile - chemistry; Biological and medical sciences; Cardiomyopathies - complications; Chromatography, Gas; Drug intoxications. Doping; Fatal Outcome; Gas Chromatography-Mass Spectrometry; Gastrointestinal Contents - chemistry; Humans; Male; Medical sciences; Olanzapine; Pharmacology. Drug treatments; Pirenzepine - analogs & derivatives; Pirenzepine - analysis; Pirenzepine - blood; Pirenzepine - cerebrospinal fluid; Pirenzepine - urine; Vitreous Body - chemistry; Human; Sulfur nitrogen heterocycle; Biological fluid; Chemical analysis; Olanzapine; Liquid liquid extraction; Coupled method; Neuroleptic; Psychotropic; Drug intoxication; Postmortem; Forensic aspect; Tricyclic compound; Autopsy material; Gas chromatography; Sample preparation; Antipsychotic; Death; Aromatic compound; Piperazine derivatives; Mass spectrometry; Quantitative analysis
• ISSN: 0146-4760; 1945-2403
• DOI: 10.1093/jat/22.7.605

Olanzapine, a new antipsychotic agent, was approved by the U.S. Food and Drug Administration in 1996 for use in the treatment of schizophrenia. It is structurally similar to clozapine, has a low incidence of extrapyramidal effects, and is effective in treating both the positive and negative symptoms of schizophrenia. This paper describes the determination of olanzapine in biological specimens obtained from the autopsy of a 35-year-old white male found dead in bed at a psychiatric facility. In the months prior to his death, the deceased was prescribed multiple medications, including olanzapine. Olanzapine was identified qualitatively by full scan gas chromatography-mass spectrometry, with quantitative analysis performed by liquid-liquid extraction followed by dual-column gas chromatography. The following concentrations were determined in the specimens analyzed: heart blood, 550 ng/mL; bile, 6346 ng/mL; and gastric contents, 157 ng/mL. Vitreous humor, cerebrospinal fluid, and urine specimens were negative. Although steady-state plasma concentrations of 10-25 ng/mL olanzapine have been reported, effective levels are known to be highly variable and a plasma concentration of 300 ng/mL has been tolerated without adverse effects. Based upon the autopsy, toxicological findings, and case investigation, the cause of death was determined to be intramyocardial arteriosclerosis with severe stenosis of the nodal artery due to hypertensive cardiovascular disease, and the manner was natural.