A case of lacosamide and mirtazapine self-poisoning.

Lacosamide is a relatively new antiepileptic drug that exerts its anticonvulsant effect by selectively inactivating sodium channels. Since its launch, it has been used widely for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal blood concentrations. Here, we report a case of drug poisoning following simultaneous high-dose self-administration of lacosamide and mirtazapine. We developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to determine the concentrations of lacosamide and mirtazapine in cadaveric blood, urine and liver. Calibration curves showed good linearity (r2 > 0.995), and our method enabled repeatable and accurate quantification, with intra- and inter-assay coefficients of variation not exceeding 10.9 % and 12.8 %, respectively, for each target drug. We used the method to measure the drug concentrations in the blood of a dead victim and found a lacosamide concentration of 91.9 µg/mL and a mirtazapine concentration of 12.0 µg/mL. The blood mirtazapine concentration was in the lethal range, and that of lacosamide was about 10 times the therapeutic range. The synergistically central nervous system depressive and cardiotoxic effects of these drugs may have contributed to the cause of death. We concluded that the cause of death in this case was lacosamide and mirtazapine poisoning.

Simultaneous quantification of 2-aminothiazoline-4-carboxylic acid and 2-aminothiazoline-4-oxoaminoethanoic acid utilizing chemical derivatization followed by liquid chromatography-tandem mass spectrometry.

Detecting cyanide compounds in postmortem blood samples is an important matter in forensic science because cyanide is often used as a poison for murder or suicide. However, the direct analysis of cyanide itself has practical limitations because of cyanide's volatility and short half-life at ambient temperature. Here, we focused on the relatively stable cyanide metabolites 2-aminothiazoline-4-carboxylic acid (ATCA) and 2-aminothiazoline-4-oxoaminoethanoic acid (ATOEA) as potential markers of cyanide exposure. We developed an analytical method that uses chemical derivatization of the target compounds with 4-bromoethyl-7-methoxycoumarin followed by liquid chromatography coupled with electrospray ionization-tandem mass spectrometry. The recovery rates for pretreatment and calibration curve linearities were good in the concentration range of 20-1000 ng/mL. Using our approach, we were able to detect and quantify both ATCA and ATOEA concentrations in postmortem blood samples, and in our samples the ratio of ATCA and ATOEA was in the range of 4.5-19.1. To our knowledge, this is the first time ATOEA has been successfully detected in human blood samples. In addition, we found that ATCA and ATOEA concentrations were both significantly higher in the blood of fire victims than in the blood of individuals with a non-fire-related cause of death. Also, we found that there was a significant positive correlation between ATCA concentrations and ATOEA concentrations. Together, our present data suggested that ATCA and ATOEA are both potential markers of cyanide exposure.