The purpose of the paper was to establish pathomorphological changes in human brain structures in chronic alcohol and combined (alcohol consumed with surrogates, psychoactive, and medicinal substances) intoxication and the possibility of their differential diagnosis. Materials and methods. The following were studied in detail: sensorimotor cortex, medulla oblongata, cerebellum, thalamus, substantia nigra, as well as pericellular and perivascular oedemata in persons who had died from chronic alcohol or combined intoxication, according to 140 forensic medical examination reports and medical history with histological and pathomorphological data. In the cortex, medulla oblongata, and cerebellum, severe pathological forms of neurons (anucleated cells, shadow cells, and dark cells) were selectively studied and counted. Homeostasis parameters in the microcirculatory bed were examined. As controls, we used data of people who had died as a result of various injuries that caused shock or blood loss. Staining was performed with haematoxylin and eosin, according to Nissl and according to Spielmeyer. The results of the research showed that in combined intoxication, the lungs are involved in the pathological process. The number of affected neurons in the brainstem, cerebral cortex, and cerebellum in combined intoxication was statistically significantly higher than that in the control samples. This pathology was also observed in chronic alcohol intoxication; however, the difference from the control samples was insignificant. In chronic alcohol intoxication, the cardiac type of thanatogenesis in the form of alcoholic cardiomyopathy prevails, while in combined intoxication, the pulmonary-cerebral and cerebral types of thanatogenesis are more common. Changes in the brain in combined intoxication are mainly the result of impaired haemodynamics of the microcirculatory bed in the alveoli, as well as of a direct neurotoxic effect of ethanol on the brain; thanatogenesis in this case is pulmonary-cerebral.
Background. The problem of determining the fact of acute and lethal poisoning with clobazam is still an urgent task of analytical toxicology. The medicinal substance clobazam belongs to the group of benzodiazepines, which is included in the list of psychoactive substances whose turnover is limited, since it has a high toxicity profile in overdose and abuse.
Aims. To propose a simple, reliable and sensitive technique for the identification of clobazam and its metabolite in urine by the modern HPLC-QqQ-MS/MS method.
Materials and methods. We have described a simple and sensitive HPLC-QqQ-MS/MS method for qualitative determination of clobazam in urine.
Results. According to the results of the study, the retention time in the selected chromatography conditions for clobazam was 5.17 minutes, and its metabolite (norclobazam) found in urine was 4.56 minutes. The base peak for clobazam is 259 m/z, and for norclobazam it is 245 m/z.
Conclusion. For the first time, a study is presented, which provides a validated method of chemical-toxicological examination for poisoning with clobazam by HPLC-MS /MS, tested both on a model mixture and on a real biological matrix of the patient's urine after taking clobazam. This technique can be used as a confirmatory research method and is an addition to the clinical picture in forensic medical examination.
Keywords: clobazam, HPLC-QqQ-MS / MS, detection, urine sample preparation
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.