Forensic Toxicokinetics And Histopathological Observation Of Zopiclone

BACKGROUND:Zopicclone,a new generation of pyrrolidone sedative and hypnotic drugs,has hypnotic,sedative,anti-anxiety,muscle relaxant and anticonvulsive effects.It has gradually replaced benzodiazepine for the treatment of sleep problems because of its fast effect,strong effect and minimal adverse reactions.Early studies have shown that zopicron is a sleeping drug with no serious side effects and has excellent clinical effects.However,with the passing of time and the extensive use of zopicron,the harm of zopicron gradually emerges and is understood and valued by people.In foreign countries,death cases related to zopiclone occur from time to time;In recent years,some cases of suicide and anaesthesia murder by zopiclone often appear in China.However,most studies on zopiclone at home and abroad focus on pharmacodynamics,pharmacokinetics,mechanism of action and determination of zopiclone in the body,and there are few reports on the forensic toxicokinetics and histopathology of zopiclone,which need further systematic study.This paper intends to explore the postmortem redistribution(PMR)and histopathology of the dead to infer the contents of zopicron in the body at the time of death and the effects of zopicron on human beings.This paper will provide some references for the selection of examination materials for postmortem examination and the identification of the causes of death.Finally,the application of postmortem redistribution in inferring the time of death is discussed.OBJECTIVE:1.Determination of different time of death of zopiclone infected rat heart,lung,liver,spleen,kidney and brain of zopiclone content,get zopiclone again after the death of distribution,for autopsy selection for examination in the extraction of the site to provide the reference,speculated that the deceased died at the same time in the content of zopiclone,inference to the cause of death for help.2.Detection of zopiclone in the liver of poisoned rats with zopiclone changes in cryopreservation,to learn the law of change,in order to obtain the autopsy extract liver zopiclone content of the accurate value,to provide reference for the identification of the cause of death,at the same time to provide advice for the detection of preservation;3.Histopathological observation was conducted on the lungs,liver,spleen,kidney and brain of zopiclone poisoned rats,to explore the influence of zopiclone on the tissue structure of the body,so as to provide reference for the determination of zopiclone poisoning and provide help for the detection of the cause of death.METHODS:1.Postmortem redistribution: 36 male SD rats,and randomly divided into 6 groups,each group of 6,with a quarter LD50 dose lavage(750 mg/kg),2 h executed immediately after the cervical dislocation,put to death after supine placed at room temperature(25 ℃)conditions,respectively after the death of 0 h,6 h,12 h,24 h,48 h,72 h anatomical extraction in the rat heart,lung,liver,spleen,kidney,and brain,the viscera extraction processing or placed on immediately-20 ℃ cryopreservation waiting for inspection.The contents of zopiclone were determined by ultraviolet spectrophotometry.2.Preservation experiment: six male SD rats,weighing 300±20 g,were added into suspension of sodium carboxymethyl cellulose and water to mix the standard substance of zopicron,which was accurately weighed 1/4 LD50,and the corresponding rats were poisoned by gavage with absorbed solvent.Immediately executed after 2 h,extraction of rat liver for 0.5 g zopiclone content detection,save the rest for examination in-20 waiting for inspection.Liver was extracted and weighed ℃for detection at 15 d,30 d,45 d,60 d and 90 d after freezing.3.Histopathological observation: 6 male SD rats were given a dose of 1/4 LD50(750 mg/kg)by intragastric administration.The symptoms of rats were observed after intragastric administration.If the rats died within 24 h,the heart,lung,liver,spleen,kidney and brain of the rats were directly dissected.If the rats were not dead,the rats were sacrificed by cervical dislocation method at 24 h.After the rats were sacrificed,the rats’ hearts,lungs,livers,livers,kidneys and brains were extracted and fixed with formalin solution for further examination.RESULTS:1.The distribution at the time of death: the content of zopicron in each organ at 0h after death was in the order of lung,liver,kidney,heart,spleen and brain;2.Postmortem redistribution: the content of zopicron in the heart increased at 0~12 h,decreased at 12~24 h,and increased at 24~72 h,but the overall trend was gentle at 24~72 h.The overall trend of lung decreased from 0 to 72 h.The overall trend of liver increased.The overall trend of spleen increased from 0 to 12 h,decreased from 12 to 24 h,and increased from 24 to 72 h.The kidney increased at 0~12 h,decreased at 12~24 h,and increased at 24~72 h.The brain increased at 0~12 h,decreased at 12~24 h,and increased at 24~72 h,but the change was small at 24~72 h.;3.In case-20 ℃ cryopreservation,liver of zopiclone content exist evident in the downward trend;4.Zopiclone-poisoned rats had cerebral edema,pulmonary hyperemia,hepatic scattered steatosis,hyperemia,glomerular hyperemia and congestion of multiple organs.CONCLUSION:1.Postmortem redistribution exists in zopiclone,and attention should be paid to the inference of the cause of death of the deceased with zopiclone poisoning;2.In the early stage,the content of zopiclone in liver and lung is relatively high.If the time of death is short,the detection effect of lung and liver extraction is better;In general,heart and brain zopiclone content change is small,if death for a long time,should measure analysis to extract the heart and brain,reduce the influence of redistribution after death,and improve the accuracy of the death reasons,and the analysis of the liver as a forensic toxicology,commonly used for examination the zopiclone content increased,affect the death reasons,need to improve;3.In-20 ℃ cryopreservation cases,liver of zopiclone content is evident in the downward trend,should be tested as soon as possible,if kept for a long time,should be considered content changes,or use more small effect way of save;4.Zopiclone-poisoned rats had cerebral edema,hepatic steatosis,edema and renal edema,which was of certain reference value for the inference of the cause of death.