A Tissue Distribution Study of Propafenone in an Intentional Fatal Poisoning Case.

Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients' admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology.

Unusual concentration of tramadol detected in cadaver in the last stage of decomposition and in fly larvae in the immediate vicinity: case report and literature review.

Determination of the manner and cause of death from skeletal remains is almost always very difficult and can be a challenge for medical examiners. At the end also on skeletal remains, it is possible to assess mechanical, chemical, and thermal injuries, although it can be usually impossible. Possibilities to analyze biological material for the presence of drugs are also limited. The present study describes a case of a homeless man's skeletal remains on which a large number of fly larvae were found. Unusually high concentration of tramadol (TML) in the bone marrow (BM) = 4530 ng/g, muscle (M) = 4020 ng/g, and fly larvae (FL) = 280 ng/g was detected using a validated GC/MS method. In all analyzed samples, caffeine and N-desmethyltramadol (except BM) were qualitatively determined. Autopsy findings and toxicological analyses of the BM suggested that the cause of death could probably be intoxication by TML. It is apparent from the reviewed literature that analysis of TML in the late stages of decomposition of human body is rarely performed. Literature is predominantly focused on animal studies. Thus, TML concentrations analyzed in BM, M, or FL could be found helpful in relation to evaluation of intoxication by this substance. However, the significance of the results obtained in the presented study should be confirmed by further analyses of BM, M, or FL, where TML would be proved in lethal concentration in the blood.

Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity.

Biologically active taxanes, present in small- to medium-sized evergreen conifers of various Taxus species, are widely used for their antioxidant, antimicrobial and anti-inflammatory effects, but mostly for their antitumour effects used in the treatment of solid tumours of the breast, ovary, lung, bladder, prostate, oesophagus and melanoma. More of the substances found in Taxus plant extracts have medical potential. Therefore, at the beginning of this review, we describe the methods of isolation, identification and determination of taxanes in different plant parts. One of the most important taxanes is paclitaxel, for which we summarize the pharmacokinetic parameters of its different formulations. We also describe toxicological risks during clinical therapy such as hypersensitivity, neurotoxicity, gastrointestinal, cardiovascular, haematological, skin and renal toxicity and toxicity to the respiratory system. Since the effect of the drug-form PTX is enhanced by various Taxus spp. extracts, we summarize published clinical intoxications and all fatal poisonings for the Taxus baccata plant. This showed that, despite their significant use in anticancer treatment, attention should also be focused on the risk of fatal intoxication due to ingestion of extracts from these plants, which are commonly found in our surroundings.

Ayahuasca as a Decoction Applied to Human: Analytical Methods, Pharmacology and Potential Toxic Effects.

Ahyahuasca is a term commonly used to describe a decoction prepared by cooking the bark or crushed stems of the liana Banisteriopsis caapi (contains ß-carbolines) alone or in combination with other plants, most commonly leaves of the shrub Psychotria viridis (contains N,N-dimethyltryptamine-DMT). More than 100 different plants can serve as sources of ß-carbolines and DMT, which are the active alkaloids of this decoction, and therefore it is important to know the most accurate composition of the decoction, especially when studying the pharmacology of this plant. The aim was to summarize the latest sensitive methods used in the analysis of the composition of the beverage itself and the analysis of various biological matrices. We compared pharmacokinetic parameters in all of the studies where decoction of ayahuasca was administered and where its composition was known, whereby minimal adverse effects were observed. The therapeutic benefit of this plant is still unclear in the scientific literature, and side effects occur probably on the basis of pre-existing psychiatric disorder. We also described toxicological risks and clinical benefits of ayahuasca intake, which meant that the concentrations of active alkaloids in the decoction or in the organism, often not determined in publications, were required for sufficient evaluation of its effect on the organism. We did not find any post-mortem study, in which the toxicological examination of biological materials together with the autopsy findings would suggest potential lethality of this plant.