AbstractQuetiapine fumarate (Seroquel®) is an atypical antipsychotic dibenzothiazepine derivative. Due to its extensive hepatic metabolism and low level of unchanged excretion (< 1%) the routine toxicological drug-screening analyses of urine often leads to false negative results. In the present study, we report that a newly identified metabolite of quetiapine, N-desalkylquetiapine, can be used as an indicative marker of quetiapine-intake in urine using common GC-MS screening procedure. The structure of the mentioned metabolite was solved from the mass-spectrum obtained and the quetiapine presence was proved by consequent HPLC plasma analysis.

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Butyrylcholinesterase (BChE) is synthesized in the liver and found in high concentrations in blood plasma, liver, heart, pancreas, vascular endothelium, skin, brain white matter, smooth muscle cells and adipocytes. BChE is a non specific enzyme that hydrolyzes different choline esters (succinylcholine, mivacurium) and many other drugs such as aspirin, cocaine and procaine. The enzyme is also considered as a bioscavenger due to its ability to neutralize the toxic effects of organophosphorus compounds (nervous system fs agents) such as soman. BChE displays several polymorphisms that influence its serum activity; therefore they could determine the individual sensitivity to chemical nerve agents. In this study, we investigated the correlation between BChE variants and the degree of enzyme inhibition and reactivation after soman application on blood samples of 726 individuals. The blood samples of individuals expressing abnormal variants, were more sensitive to soman compared to variants of homozygotes and heterozygotes for U-allele. We found significant differences in the degree of enzyme reactivation between different variants (with and without U-presence).

We hypothesized that Tabun poisoning, as well as other organophosphorous treatment, cause specific organs' oxidative changes that have not previously been substantiated investigated. In this regard, a marker for nitrosative-oxidative stress in the main haemodynamic organs (heart and kidney) could reveal the existence of such changes. In this study, for the first time we studied the nitrosative/oxidative stress in heart and kidney after acute Tabun (Ethyl N,N- Dimethylphosphoramidocyanidate) poisoning measuring by immunohistochemistry the expression of 3-nitrotyrosine--a marker for nitrosative-oxidative stress. We investigated nitrotyrozine expression in three different groups of animals (with at least 3 animals in each group): the first group was treated with 0.5 LD50 Tabun and organs were collected after 24 h; the second group received vehicle for the same period; in the third group a highly specific re-activator was applied immediately after Tabun application. Heart and kidney were collected after 24 h. The levels of nitrotyrozine production significantly increased (more than 3 times) in cardiomyocytes after Tabun. The application of re-activator slightly reduced these levels not reaching the basal heart levels. Nitrotyrozine expression in kidney increased more than 2 times after Tabun and application of re-activator did not change it significantly. In conclusion, our study evidently demonstrated that Tabun trigger oxidative-nitrosative stress in heart and kidney and these cellular effects should be protected by an additional anti-oxidant therapy, since acetylcholinesterase re-activator is not efficient in this manner.

AbstractThe simultaneous application of intravenous fat emulsion and charcoal hemoperfusion in the case of severe quetiapine poisoning is described. The initial blood concentration of quetiapine was 5.9 µg/mL and rapid deterioration in the patient status was observed. When a lipid emulsion was infused a fast blood pressure recovery occurred which allows to perform extracorporeal clearance using charcoal hemoperfusion. At the end of the procedure the quetiapine concentration was decreased down to 1.5 µg//mL and fast recovery of the patient was observed.