|SOFT - TIAFT 1998||Poster Session 3||Thursday October 8, 1998|
THIRTY CASE STUDIES INVOLVING POSTMORTEM TISSUE DISTRIBUTIONS OF OLANZAPINE (ZYPREXA®)|
Daniel T. Anderson
Los Angeles County Department of Coroner, 1104 North Mission Road, Los Angeles, CA 90033, U.S.A.
|Olanzapine, introduced onto the market in late 1996, is a thienobenzodiazepine derivative which displays efficacy in patients with schizophrenia and related psychoses. To date, the literature provides limited information about therapeutic blood concentrations and no information about postmortem blood levels or tissue distributions. During 1997 & 1998, the Los Angeles County Department of Coroner Toxicology Laboratory encountered thirty cases where olanzapine was detected and postmortem tissue distributions were determined.
The analysis of olanzapine from postmortem specimens (2 ml sample size) consisted of an n-butylchloride basic extraction procedure with screening and quantitation on a GC/NPD. Linearity was achieved from 0.025 mg/L to 3.0 mg/L with the limit of quantitation being 0.01 mg/L. Confirmation of olanzapine was performed on a GC/MS by comparison with an pure analytical standard.
The tissue distribution of olanzapine are in the following concentration ranges with the number of cases associated: Heart blood 0.01 - 4.8 mg/L (n = 29), Femoral blood 0.01 - 1.6 mg/L (n = 24), Vitreous 0.01 - 2.1 mg/L (n = 6), Liver 0.01 - 13 mg/kg (n = 23), Bile 0.02 - 8.4 mg/L (n = 17), Urine 0.03 - 16 mg/L (n = 25), and Gastric 0.001 - 62 mg total (n = 21). A very important point was observed; with any repeat blood analysis, the concentration of olanzapine decreased substantially, virtually becoming non-detectable over time. Because of this degradation process, the olanzapine concentration must be measured as soon as possible. The case studies reviewed include the decedent's history, postmortem tissue distribution, medical evidence, and cause/mode of death. The information presented about olanzapine, a new anti-psychotic drug, can be useful for postmortem comparisons.