Distribution of Mirtazapine (Remeron(R)) in Thirteen Postmortem Cases

Abstract

Mirtazapine is a new antidepressant agent that entered the United States market in April 1996. To date, the literature provides limited information about therapeutic blood concentrations and virtually no information about postmortem levels. The Los Angeles County Coroner's Toxicology Laboratory has encountered 13 cases where postmortem tissue distributions of mirtazapine were determined. The analysis of mirtazapine from postmortem specimens (2-mL sample size) consisted of an n-butylchloride basic extraction procedure with identification and quantitation on a gas chromatograph-nitrogen-phosphorus detector. Linearity was achieved from 0.025 mg/L to 3.0 mg/L with a limit of quantitation of 0.025 mg/L. Confirmation of mirtazapine was performed on a gas chromatograph-mass spectrometer by comparison with a pure analytical standard. The tissue distribution of mirtazapine are in the following concentration ranges: heart blood 0.03-0.57 mg/L (13 cases), femoral blood 0.04-0.24 mg/L (9 cases), vitreous 0.06-0.10 mg/L (3 cases), liver 0.32-2.1 mg/kg (12 cases), bile 0.40-6.6 mg/L (7 cases), urine 0.12-2.5 mg/L (11 cases), kidney 0.23 mg/kg (1 case), spleen 0.17 mg/kg (1 case), and gastric 0.001-2.7 mg total (9 cases). Mirtazapine was not implicated in the cause of death in any of the 13 cases studied. These cases are being presented to aid the forensic toxicologist in the evaluation of postmortem mirtazapine levels.

Enantioselective separation of the novel antidepressant mirtazapine and its main metabolites by CEC

“…As can be observed, good linearity was achieved over the studied concentration ranges. To the best of our knowledge, only two papers were found concerning the determination of MRT in urine samples in which the mean values were 0.62 and 1.31 mg/mL, respectively [41,42]. These data were in accordance with the linearity range studied.…”

Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h

“…According to Hilberg et al [7] all molecules with a Vd equal to or greater than 3 L/kg are liable to undergo postmortem redistribution. However there are some molecules which appear to be an exception to this rule such as mirtazapine a drug with a Vd of ~5L/kg has not been shown to exhibit any postmortem redistribution [8]. If the mechanisms governing postmortem redistribution could be defined this would help the interpretation of postmortem drug levels.…”

Enantiomeric separation of mirtazapine and its metabolites by nano‐liquid chromatography with UV‐absorption and mass spectrometric detection

“…Some methods are reported in the literature [10, 13 -20] for the analysis of MIR in human plasma using LC, with spectrophotometric [14], spectrofluorimetric [10,13,15,17,18] or MS detection [19,20], or GC-MS [16]. A few of these methods determine DEMIR [14,17] and 8-OH-MIR [19] as well; however, only three of them carry out a chiral determination of MIR, alone [15,18] or together with the metabolites [19] using cellulose or protein and vancomycin column, respectively.…”