氯胺酮在家兔死后体内的弥散研究

目的研究氯胺酮在大白兔体内死后弥散过程和再分布机制。方法 48只实验大白兔随机分为8组,采用缺氧处死后以150mg/kg氯胺酮灌胃,尸体仰卧位于室温下放置;在0~96h内分8个时间点各解剖1组,提取体液和脏器组织样品;采用GC/MS法定性结合GC-NPD法定量检测样品中氯胺酮含量,并计算心血/外周血中氯胺酮含量的比值。结果大白兔死后氯胺酮灌胃尸体放置96h内,脑、尿液、玻璃体液、左上/下肢肌肉样本中均未检测到氯胺酮,心血、外周血、心肌、脾、肾、肝、肺、胆汁中氯胺酮含量随死后时间呈动态升高的变化;其中距离胃较近的组织(如脾)较早检测到含量较高的氯胺酮,而距离较远的组织或体液中氯胺酮含量较低且较晚检测到;心血/外周血中氯胺酮含量比值为1.73。结论氯胺酮在家兔体内存在死后再分布,从胃到器官组织、心血顺浓度梯度弥散是主要机制。脑、玻璃体液、尿液、肢体肌肉不受死后弥散的影响,可作为生前服毒与死后染毒氯胺酮的鉴别依据。     

Analysis of 2,4-Dinitrophenol in Postmortem Blood and Urine by Gas Chromatography–Mass Spectrometry: Method Development and Validation and Report of Three Fatalities in the United States

2,4-dinitrophenol (2,4-DNP) is a compound used in the early 1900s as a weight-loss drug but later prohibited due to its severe adverse effects, including death. It has however been attracting interest, due to its weight-loss properties, and appears to be re-emerging in forensic casework. As 2,4-DNP is available for use in industry and as a pesticide and easily accessible online, the dissemination of this drug can be fast. The compound exerts its effects through inhibition of ATP synthesis, and corresponding thermogenic energy loss which can be fatal. A method for qualitative and quantitative analysis of 2,4-DNP in blood and urine specimens using GC-MS with hydrogen as carrier gas is described. The method was validated and displayed acceptable performance parameters with linearity (R² higher than 0.998), inter-assay imprecision (lower than 10.6%), intra-assay imprecision (lower than 10.7%), and extraction efficiency (92.1%). Stability of 2,4-DNP in blood and urine was studied, and the drug was stable up to 30 days refrigeration or frozen. Six cases in United States suspected to be related to 2,4-DNP were analyzed. Three cases were found to be positive for 2,4-DNP. Concentrations of 2,4-DNP were in the range of 61.6–220 mg/L in urine and <3–114 mg/L in blood. Based on our findings, we suggest that medical examiners and forensic toxicologists be aware of the reappearance of 2,4-DNP, including this compound as a target in death investigations related to weight-loss drugs.     

死后血液流动对氯胺酮在家兔尸体内再分布的影响

目的观察分析静脉注射氯胺酮家兔死后血液流动对体内药物浓度再分布影响。方法雄性新西兰大白兔随机分为实验组2组（各24只）,对照组（8只）;实验组家兔经耳缘静脉注入40mg/kg氯胺酮,1.5h后处死,其中一组立即结扎主动脉,另一组不结扎;家兔尸体仰卧位室温下保存,分别于死后0、3、6、12、24、48、72和96h解剖并采取组织和体液样本;对照组静脉注射等量生理盐水,同样方法解剖取相同样本。所有样本采用GC/MS和GC-NPD法检测样品中氯胺酮含量。结果两个实验组家兔尸体放置96h内氯胺酮含量,除尿液各时间点与0h以及相邻时间点之间比较均有显著性差异（P〈0.05）外,两组家兔其余各类样本与0h以及相邻时间点比较均无显著性差异（P〉0.05）。除尿液外,各类样本两个实验组之间均无显著性差异（P〉0.05）;结扎组和不结扎组心血与外周血中氯胺酮含量比值分别为0.90~1.03和0.90~1.02。结论静脉注射氯胺酮家兔死后的血液流动不是体内氯胺酮发生再分布的主要机制。     

甲基苯丙胺心肌毒性的研究进展

甲基苯丙胺(MA)是近年来在我国公共场所流行滥用的成瘾性药物,俗称冰毒。目前实验研究发现,MA对人体多个系统都具有毒性作用,其中对心血管系统的毒性损害作用较为显著。临床表现上,MA中毒主要导致了以心率和血压改变为特异性表现的一系列症状,以及继发的心脏结构改变所导致的心脏损害;病理学上,MA中毒导致了心肌坏死、心肌间质炎细胞增多、心肌纤维化、心肌梗死等。法医学研究中,发现了MA急性中毒导致死亡的主要原因是MA引起的心律失常和室颤,慢性中毒的死因较多,以MA慢性中毒导致高血压、心肌病、心肌梗死等为主。MA中毒的心肌毒性的分子机制表现为心肌内多种蛋白质表达的改变。目前MA心肌毒性的机制研究较多,但仍未完全查明。本文通过对近年来MA心肌毒性研究现状进行综述,为后续研究提供参考。     

A study of drug detection in a postmortem pediatric population

At The Office of the Cuyahoga County Coroner (CCCO), Cleveland, Ohio, it is customary to perform an autopsy and conduct toxicological testing on decedents less than 19 years of age. This study provides a retrospective evaluation of drugs detected in a pediatric postmortem population between the years 1998 and 2002 (n = 730). Demographic information, cause and manner of death, and toxicological results were examined. Blacks comprised 54% of cases, males 59%, and 48% were less than one year of age or stillborn. Forty-two percent of deaths were ruled natural, 27% accident, 13% undetermined, 5% suicide, and 2% homicide. Of the 640 cases subjected to comprehensive testing, 38% of the cases were positive for at least one compound. Resuscitative/treatment drugs were detected most frequently (56% of positive results), followed by illicit drugs (26%), ethanol (11%), carbon monoxide (8%), and antihistamines (6%). Eighty-seven cases contained more than one drug. The deaths of 47 individuals were drug related (6%). In this population, it is recommended that illicit drugs and ethanol are targeted for testing, especially when limited specimens are available for analysis.     

可卡因染毒致小鼠免疫功能损伤的影响

目的考察可卡因染毒对小鼠免疫功能的影响。方法615纯系雄性小鼠20只,随机均分为实验组和对照组;实验组小鼠以30mg／kg盐酸可卡因每天1次进行腹腔连续注射,空白组给予相同量盐水同法注射盐水;第30d处死小鼠,测量体重与脏器系数,用四甲基偶氮唑蓝（MTr）法检测脾细胞、胸腺细胞与腹腔巨噬细胞（PMφs）的增殖活性;用生物活性检测法检测IL-1与IL-2的活性;用ELISA法检测IFN-γ／与TNF—α含量。结果实验组小鼠脾细胞、胸腺细胞与PMφs的增殖反应明显降低;脾细胞培养上清液中IL-2与IFN-γ活性明显降低;PMφs培养上清中IL-1与TNF—α活性明显降低;体重、脾脏与胸腺系数也明显降低;上述指标较之对照组均有显著性差异（P〈0．01）。结论在活体条件下可卡因染毒对小鼠免疫系统功能有明显抑制作用。     

从ICE看缴获毒品检验的发展趋势

当今世界缴获毒品检验使用的技术发展迅速,为促进各国相关实验室间的技术交流,国际合作测试项目(ICE)已开展多次,本文通过对ICE缴获毒品组测试结果和总体评估报告进行分析,针对国际上缴获毒品检验常用技术方法及发展趋势进行分析,希望能为相关研究和实践提供一些参考和借鉴.     

甲基苯丙胺和氯胺酮在家兔体内毒代动力学及相互影响

目的比较家兔单独静脉注射甲基苯丙胺、氯胺酮及二种药物联合静注时的毒物代谢动力学过程,评价二种药物毒代动力学的相互作用。方法单用甲基苯丙胺组以3mg/kg剂量家兔静脉注射甲基苯丙胺,单用氯胺酮组以30mg/kg剂量家兔静脉注射氯胺酮,合用组以相同剂量同时注射两种药物。分别于给药后不同时间点收集血浆标本,测定各时间点药物浓度,WinNonLin软件拟合毒代动力学房室模型并计算参数。结果甲基苯丙胺在家兔体内的毒代动力学过程呈一级动力学特征,符合单室模型,合用氯胺酮后不改变其模型类型。氯胺酮在家兔体内的毒代动力学过程呈一级动力学特征,符合单室模型,合用甲基苯丙胺后符合二室模型。结论甲基苯丙胺和氯胺酮可以相互延缓其在体内的消除过程,增加彼此在体内的吸收,从而延长作用时间。     

Possible role of pseudoephedrine and other over-the-counter cold medications in the deaths of very young children

The Philadelphia Medical Examiners Office has reported a series of 15 deaths between February 1999 and June 2005 of infants and toddlers 16 months and younger in which drugs commonly found in over-the-counter (OTC) cold medications were present. A total of 10 different drugs were detected: pseudoephedrine, dextromethorphan, acetaminophen, brompheniramine, carbinoxamine, chlorpheniramine, ethanol, doxylamine and the anticonvulsants, phenobarbital, and phenytoin. The drugs were confirmed and quantified by gas chromatography (GC)-mass spectrometry, with the exception of ethanol, which was analyzed by headspace GC and of phenobarbital and phenytoin that were quantified by GC with a nitrogen phosphorus detector. The most predominant drug was pseudoephedrine, which was found in all of the cases (blood concentration, n=14, range=0.10-17.0 mg/L, mean=3.34 mg/L) and was the sole drug detected in three cases. Acetaminophen was detected in blood from each of the five cases with sufficient sample. Other drugs (with frequency of detection) were dextromethorphan (five cases), carbinoxamine (four cases), chlorpheniramine (two cases) and brompheniramine, doxylamine, and ethanol (one case each). In the majority of the cases, toxicity from drugs found in easily available OTC medications was listed either as the direct cause of death or as a contributory factor. The manner of death was determined to be natural in only two of the cases. This postmortem study supports previous evidence that the administration of OTC cold medications to infants may, under some circumstances, be an unsafe practice and in some cases may even be fatal. The treating physicians and the general public need to be made more aware of the dangers of using OTC cold medications to treat very young children so that these types of tragedies might be avoided.     

Relationships between concentrations of cocaine and its hydrolysates in peripheral blood, heart blood, vitreous humor and urine

Cocaine is known to degrade in vivo and in vitro by several hydrolytic mechanisms. A previous study found that the initial amount of cocaine added to plasma could be accounted for by summing the molar concentrations of cocaine's hydrolysis products and the cocaine remaining after hydrolysis. The present study was undertaken to investigate whether or not relationships might exist between such molar concentration sums for different postmortem bodily fluids. Determinations of cocaine, benzoylecgonine, ecgonine methyl ester, and ecgonine were performed using liquid chromatography/mass spectrometry (LC/MS/MS) with heart blood, femoral blood, vitreous humor (VH), and urine (UR). The results demonstrate a strong correlation between blood and VH concentrations (correlation coefficients of 0.88-0.94), weak correlation between the UR and blood concentrations (correlation coefficients of 0.61-0.64), and weak correlation between UR and VH concentrations (correlation coefficient of 0.59). The results demonstrate that ecgonine is a significant hydrolysate with concentrations on the same order of magnitude as benzoylecgonine. The results are consistent with rapid distribution of the parent drug and its hydrolysates in the blood and VH. The strong correlation between the blood and VH demonstrates that VH is an important medium for toxicology testing when attempting to make a determination of cocaine intoxication.     

可卡因对小鼠离体脾细胞功能的影响

目的 观察盐酸可卡因对小鼠体外培养脾细胞功能的影响.方法 采用小鼠脾细胞体外培养的方法,在细胞培养液中加入终质量浓度分别为10、20和100μg/mL的盐酸可卡因,连续培养.检测脾细胞的ConA增殖反应、IL-2、IFN-γ的活性.结果 实验组ConA诱导的小鼠脾细胞增殖反应明显降低,IL-2和IFN-γ的活性显著下降,与对照组相比较有显著性差异(P＜0.05;P ＜0.01).结论 可卡因对体外培养脾细胞功能有显著的抑制作用.     

GC/MS检验不同案件中摇头丸

目的 分析不同案件缴获的“摇头丸”主要成分和添加物,为确定“摇头丸”的合成路线、非法来源提供依据.方法 以GC/MS检测法为主要检测方法.结果 检验的14个“摇头丸”主要成分为甲基苯丙胺和咖啡因,其中含有少量的其他杂质如麻黄碱和氯胺酮等.结论 检测的14个“摇头丸”样本其中12个含甲基苯丙胺,实为冰毒成分,1个为咖啡因均不属于摇头丸.     

氯胺酮体内分布综述

氯胺酮作为一种重要的麻醉药品在临床上有着广泛的应用。近年来,其非法滥用问题日益凸显,随之而来的犯罪数量亦呈不断增长趋势。本文对氯胺酮在活体内的分布以及死后尸体内再分布等受温度、药物相互作用、邻近组织器官相互作用、尸体保存条件等因素影响进行了综述。     

芬太尼中毒死亡大白兔体内分布研究

目的建立芬太尼中毒致死的动物模型,探讨芬太尼在致死大白兔体内的分布规律。方法用6只雄性大白兔按5.4mg/kg(2LD50)经耳缘静脉推注芬太尼注射液,大白兔死后迅速解剖并提取心、肝、脾、肺、肾、脑、肌肉、睾丸、胃、心血、周围血、胆汁和尿液,用正己烷∶乙醇(20∶1)萃取,利用UPLC-MSn法检测各组织和体液中芬太尼含量,使用SPSS15.0进行方差分析,均数两两比较的SNK法进行统计分析。检验水准为α=0.05。结果实验大白兔给药后1min出现颈项强直、四肢抽搐等中毒症状,平均4.7min因呼吸抑制而死亡。死后肺内芬太尼含量最高,其次是肾和心,而尿液中含量较低。结论本实验的结果与相关案例报道基本吻合,提示肺、肾和心脏是芬太尼中毒案件鉴定的理想检材,芬太尼在致死大白兔体内的分布规律可为相关案件的鉴定提供一定的依据。