SOFT - TIAFT 1998 Poster Session 3 Thursday October 8, 1998

Barry S. Levine, S.C. Wu and John E. Smialek

Office of the Chief Medical Examiner, State of Maryland, 111 Penn St., Baltimore, MD 21201, U.S.A.

Olanzapine is a benzodiazepine analog sold in the Unites States under the trade name Zyprexa®. It is structurally similar to clozapine and is used to treat schizophrenia. It is reported to have fewer extrapyramidal effects than phenothiazines or butyrophenones. After a single 12.2 mg dose, peak plasma concentrations averaged 0.011 mg/L. The therapeutic steady state concentrations ranged from 0.009 to 0.023 mg/L. Olanzapine is extensively metabolized by demethylation, hydroxylation, N-oxide formation and glucuronidation.

Over a 5-month period, olanzapine was identified in 7 cases investigated by the Office of the Chief Medical Examiner. Olanzapine is extracted under alkaline conditions and chromatographs without derivatization. On a phenylmethyl silicone column, olanzapine has a retention time between nordiazepam and flurazepam. Olanzapine was confirmed in all 7 cases by full-scan electron impact gas chromatography/mass spectrometry; the drug was quantitated using gas chromatography-nitrogen-phosphorus detection.

Five of the 7 cases had causes of death other than olanzapine intoxication; the blood olanzapine concentrations in these cases were between 0.04 and 0.27 mg/L. Urine concentrations were between 0.19 and 0.50 mg/L (n = 3). The cause of death in the sixth case was combined methadone and olanzapine intoxication; the blood and urine olanzapine concentrations were 0.16 and 1.3 mg/L, respectively. The cause of death in the seventh case was olanzapine intoxication; the blood and urine olanzapine concentrations were 0.98 and 28 mg/L respectively.

These data indicate that the "postmortem therapeutic range" for olanzapine is higher than the reported antemortem steady state plasma concentrations. In addition, there was some evidence that olanzapine is unstable in stored blood. In the olanzapine intoxication case, the same blood specimen was analyzed about one month later after storage at 4oC and was found to have an olanzapine concentration of 0.16 mg/L. Decreases were also observed after re-analysis of the other blood specimens containing olanzapine.

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