|SOFT - TIAFT 1998||Poster Session 3||Thursday October 8, 1998|
MIRTAZAPINE (REMERON®): DETECTION OF A NEW ANTIDEPRESSANT IN POSTMORTEM CASES|
Eric S. Lavins, Heather M. Wogoman and Amanda J. Jenkins
Cuyahoga County Coroner's Office, 2121 Adelbert Road, Cleveland, OH 44106 U.S.A.
|Mirtazapine, an analog of mianserin, is a piperazino-azepine compound approved by the U.S. Food and Drug Administration in 1996 for use in the treatment of depression. It has a tetracyclic structure unrelated to selective serotonin reuptake inhibitors, tricyclic antidepressants or monoamine oxidase inhibitors. Mirtazapine administration results in increased release of norepinephrine and serotonin due to blockade of central presynaptic alpha2-adrenergic receptors. After a 15 mg/d dose, peak steady state plasma concentrations of 27-51 ng/mL are reached in approximately 5 days. After a 75 mg/d dose, peak steady state plasma concentrations in the range of 137-225 ng/mL are achieved.
We report 2 postmortem cases in which mirtazapine was detected in heart blood specimens: Case #1- An 82 year old white female was found by nursing staff on the floor of her bedroom at a nursing care facility. Her medications included diet supplements, albuterol, donepezil and mirtazapine. An autopsy was not performed but heart blood was submitted for toxicological analysis. Case #2- A 70 year old white male was found by nursing staff on the bathroom floor at a nursing facility. Medications included alprazolam, diltiazem and mirtazapine. An autopsy was not performed but heart blood was submitted for toxicological analysis.
Mirtazapine was identified by dual column (RTx-50 and RTx-200) gas chromatography with nitrogen phosphorus detection (HP 6890 GC) after a basic liquid-liquid extraction. Promazine was utilized as the internal standard. Quantitation was achieved by assaying calibrators (200-2000 ng/ml) concurrently with case specimens (r > 0.999). Confirmation was achieved by full scan electron impact gas chromatography/mass spectrometry using an HP 5970 MSD with a DB-5 column.
Mirtazapine chromatographed well on the RTx-50 column, with a relative retention time of 0.978 min, eluting near benztropine. By GC/MS, the base peak of mirtazapine was m/z 195, with a molecular ion of m/z 265, and other prominent ions at m/z194, 208 and 43. The heart blood specimens from each case were subjected to comprehensive toxicological analysis. Mirtazapine was the only drug detected. The mirtazapine blood concentration in case #1 was 280 ng/ml and for case #2, 100 ng/ml. Although the mirtazapine concentration in case #1, was slightly higher than previously reported therapeutic levels, the cause of death was determined to be atherosclerotic heart disease, and the manner, natural.