Postmortem distribution of 3,4-methylenedioxy-N,N-dimethyl-amphetamine (MDDM or MDDA) in a fatal MDMA overdose

Abstract

In this manuscript, a newly identified compound, 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDM or also called MDDA), was quantified. The substance was identified in the biological specimens of a 31-year-old man who died following a massive 3,4-methylenedioxymethamphetamine (MDMA) overdose. In addition, the postmortem distribution of the identified substance in various body fluids and tissues was evaluated. For MDDM quantitation, a formerly reported and validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method was adapted. The following quantitative results of the MDDM quantitation were obtained: Femoral blood, aorta ascendens, and right atrial blood contained 2.5, 21.7, and 11.6 ng MDDM/ml, respectively. In left and right pleural fluid and pericardial fluid, concentrations of 47.0, 21.7, and 31.9 ng/ml, respectively, were found. MDDM levels in urine, bile, and stomach contents were 42.4, 1,101, and 1,113 ng/ml, respectively. MDDM concentrations in lungs, liver, kidney, and left cardiac muscle ranged from 12.8 to 39.8 ng/g, whereas these levels were below the limit of quantitation (< LOQ) in right cardiac and iliopsoas muscle. In conclusion, for the first time, MDDM was unambiguously identified in a fatal MDMA overdose. MDDM was probably present as a synthesis by-product or impurity in the MDMA tablets, which were taken in a huge amount by the victim, or MDDM was ingested separately and prior to the MDMA overdose. A third option, i.e., the eventual formation of MDDM as a result of postmortem methylation of MDMA by formaldehyde, produced by putrefaction processes or during storage under frozen conditions, is also discussed. The MDDM levels, substantiated in various body fluids and tissues, are in line with the distribution established for other amphetamine derivatives and confirm that peripheral blood sampling, such as that of femoral blood, remains the "golden standard".

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

“…Thus, an elevated central blood level may somehow reflect the drug concentration in the heart. The central to peripheral blood concentration ratios have been investigated for various compounds [135][136][137][138] and their values are listed in the table in supplementary material. As drugs diffuse not only from the myocardium but also from other surrounding organs, these data in some cases may be misleading.…”

Comparative &lt;i&gt;in Vitro&lt;/i&gt; Studies of the Metabolism of Six 4-Substituted Methamphetamines and Their Inhibition of Cytochrome P450 2D6 by GC-MS with Trifluoroacetyl Derivatization

“…Designer drugs are a serious problem worldwide, especially among young people, and in some cases they have resulted in fatal poisoning [1][2][3][4][5][6][7]. New designer drugs are created by changing the molecular structure of an existing drug.…”

Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model

“…The depression in Ca 2+ regulatory mechanism by reactive oxygen species ultimately results in intracellular Ca 2+ overload and cell death [21]. Studying the problem is difficult because different experimental animals respond differently both from other models and from humans [11,17]. In general, the acute effects of MDMA seem to be more or less the same in most animal models, but the models diverge widely when it comes to their ability to produce the changes induced by chronic exposure [27].…”