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

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".

Interpretation of a 3,4-methylenedioxymethamphetamine (MDMA) blood level: discussion by means of a distribution study in two fatalities.

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy" is a currently used or abused designer drug and fatalities are frequently encountered in forensic practice. However, the question remains open whether an MDMA blood level can be toxic or even potentially lethal. In order to provide insight in the interpretation of a detected MDMA concentration, the distribution of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) in various body fluids and tissues was studied and discussed in two different fatalities. Apart from peripheral blood samples (such as femoral and subclavian blood), various blood samples obtained centrally in the human body and several body fluids (such as vitreous humour) were examined. In addition, various tissues such as cardiac muscle, lungs, liver, kidneys, and brain lobes were analysed. In contrast to the peripheral blood levels, high MDMA and MDA levels were found in cardiac blood and the majority of the organs, except for the abdominal adipose tissue. The high concentrations observed in all lung lobes, the liver and stomach contents indicate that post-mortem redistribution of MDMA and MDA into cardiac blood can occur and, as a result, blood sampled centrally in the body should be avoided. Therefore, our data confirm that peripheral blood sampling remains "the golden standard". In addition, a distinct difference in peripheral blood MDMA concentrations in our two overdose cases was established (namely 0.271 and 13.508 microg/ml, respectively). Furthermore, our results suggest that, if a peripheral blood sample is not available and when putrefaction is not too pronounced, vitreous humour and iliopsoas muscle can be valuable specimens for toxicological analysis. Finally, referring to the various mechanisms of death following amphetamine intake, which can result in different survival times (e.g. cardiopulmonary complications versus hyperthermia), the anatomo-pathological findings and the toxicological results should be considered as a whole in arriving at a conclusion.

No compound a formation with Superia during minimal-flow sevoflurane anesthesia: a comparison with Sofnolime.

UNLABELLED: There is concern about the toxicity of Compound (Co) A. Absorbents differ in the production of Co A during minimal-flow sevoflurane anesthesia. Strong alkali-free Amsorb does not produce Co A. It was our aim to study Superia, another new NaOH- and KOH-free CO(2) absorbent, in minimal-flow anesthesia, compared with KOH-free Sofnolime. After Ethics Committee approval, 14 consenting adult patients were included randomly by using Superia or Sofnolime as the CO(2) absorbent in the compact 750-mL canister of an ADU ventilator. After propofol and remifentanil administration, sevoflurane was given in oxygen and air (500 mL/min; fraction of inspired oxygen, 0.4), aiming at an end-tidal concentration of 2.3%-2.5%; ventilation aimed for 33-35 mm Hg PETCO(2). Compound A inspired (Co A(insp)) and expired (Co A(exp)) samples were taken for analysis, and canister temperatures were measured for 150 min. Statistical analysis was performed with the Friedman test or the Mann-Whitney U-test where appropriate. Correction for multiple testing was used. In the Superia group, no significant amount of Co A was formed, whereas in the Sofnolime group, maximum median (range) inspiratory values of 25 ppm (16 ppm) were found. The intergroup difference was P < 0.05. No difference was noticed between the two groups for the canister CO(2) absorbent temperature. IMPLICATIONS: During minimal-flow 2.3%-2.5% end-tidal sevoflurane, no compound A (Co A) is formed with the NaOH- and KOH-free CO(2) absorbent Superia. Although Co A values with KOH-free Sofnolime are still within reported safe limits, Superia is definitely an alternative for safe clinical practice.

Quantitative determination of n-propane, iso-butane, and n-butane by headspace GC-MS in intoxications by inhalation of lighter fluid.

This report describes a fully elaborated and validated method for quantitation of the hydrocarbons n-propane, iso-butane, and n-butane in blood samples. The newly developed analytical procedure is suitable for both emergency cases and forensic medicine investigations. Its practical applicability is illustrated with a forensic blood sample after acute inhalative intoxication with lighter fluid; case history and toxicological findings are included. Identification and quantitation of the analytes were performed using static headspace extraction combined with gas chromatography-mass spectrometry. In order to reconcile the large gas volumes injected (0.5 mL) with the narrowbore capillary column and thus achieve preconcentration, cold trapping on a Tenax sorbent followed by flash desorption was applied. Adequate retention and separation were achieved isothermally at 35 degrees C on a thick-film capillary column. Sample preparation was kept to a strict minimum and involved simply adding 2.5 microL of a liquid solution of 1,1,2-trichlorotrifluoroethane in t-butyl-methylether as an internal standard to aliquots of blood in a capped vial. Standards were created by volumetric dilution departing from a gravimetrically prepared calibration gas mixture composed of 0.3% of n-propane, 0.7% of iso-butane, and 0.8% of n-butane in nitrogen. In the forensic blood sample, the following concentrations were measured: 90.0 microg/L for n-propane, 246 microg/L for iso-butane, and 846 microg/L for n-butane.