Regional distribution of methamphetamine in autopsied brain of chronic human methamphetamine users

We measured levels of methamphetamine and those of its metabolite amphetamine in 15 autopsied brain regions of 14 human methamphetamine users. Only slight regional differences were observed in drug concentrations among the brain areas. Although, some redistribution of the drugs probably occurred postmortem, these data suggest that methamphetamine might not be preferentially retained in dopamine-rich brain areas but is heterogenously distributed in brain of chronic human users of the drug. The possible pharmacological actions of methamphetamine in both dopamine-rich and poor brain areas of chronic drug users need to be considered.     

Site-dependent postmortem changes in blood cocaine concentrations

When a forensic toxicologist interprets postmortem blood cocaine findings he usually must make assumptions regarding perimortem drug concentrations. In-vitro studies have shown that cocaine rapidly hydrolyzes in unpreserved blood, particularly at elevated temperatures. However, other studies have demonstrated site-dependent postmortem release of some drugs from tissue stores accompanied by increases in drug concentrations in the blood. This study was undertaken to investigate whether blood cocaine concentrations change in the body during the postmortem interval and, if so, to measure the direction and magnitude of the changes. In medical examiner cases in which scene investigation suggested that the decreased was a cocaine user, blood samples were collected as soon after death as possible. At autopsy, a second set of samples was collected. Analysis of paired samples by gas chromatography/mass spectrometry (GC/MS) revealed dramatic differences in the cocaine concentration. The magnitude and direction of the change appears to be site dependent. Usually, but not invariably, cocaine concentration in subclavian vein blood decreases while that in heart, aorta, and femoral vein blood increases during the interval between death and autopsy. The findings emphasize the danger inherent in attempting to estimate the concentration of cocaine in blood at the time of death from postmortem data.     

Flualprazolam distribution in postmortem samples

The constant emergence of novel psychoactive substances is troubling to both public health officials and legislators. Additionally, sufficient data collection for each new compound can take months up to years. Flualprazolam, a triazolobenzodiazepine, quickly garnered attention as a sedative drug that likely expresses adverse reactions similarly to alprazolam. This study focuses on the distribution of flualprazolam in multiple common postmortem matrices. Central blood, vitreous humor, liver homogenate, brain homogenate, gastric contents, and urine samples from death investigation cases were quantitated when available. Samples were screened with liquid chromatography quadrupole time-of-flight with limit of detection set at 4 ng/ml and quantitated on liquid chromatography tandem mass spectrometry, with concentration range from 4 to 256 ng/ml. From August 2018 to September 2020, 24 central blood samples were quantitated for flualprazolam. Central bloods of 22 cases had concentrations above the limit of quantitation. The average flualprazolam central blood concentration was 16.3 ng/ml with a median of 9.95 ng/ml (4.24–48.0). Additional analyses for unconjugated flualprazolam were performed on at a total of 15 urine samples ( = 14.4, 4.07–36.1 ng/ml), 23 brain homogenates ( = 23.2, 3.99–69.3 ng/g), 23 liver homogenates ( = 50.7, 13.6–156 ng/g), five vitreous humor samples ( = 7.70, 4.03–12 ng/ml), and 12 gastric contents samples ( = 0.36, 0.02–2.51 mg). The cause of death for 13 of the 24 cases listed flualprazolam as a contributing factor of death.     

Chloroquine distribution in postmortem cases

Chloroquine concentrations in blood and tissues were examined in overdose and non-overdose cases to determine appropriate ranges for interpretation. Twenty-nine literature overdose cases and 8 non-overdose literature cases were compared with this laboratory's findings. The results indicate significant postmortem redistribution of chloroquine. Combining this laboratory's results and the literature results indicates that using a liver concentration of 150 mg/kg as a cutoff between overdose and non-overdose concentrations properly identified 30 of the 34 published cases containing liver chloroquine and 19 of the 20 presented cases.     

Fluvoxamine distribution in postmortem cases

Four postmortem cases are reported in which the selective serotonin re-uptake inhibitor fluvoxamine was identified. Fluvoxamine was detectable using a standard alkaline drug screen, chromatographed well using a HP-1 column, and did not require derivitization for quantitation. Two of the cases reported were drug intoxications; fluvoxamine was only an incidental finding in the other 2 cases. Central and peripheral blood values are reported, as well as antemortem blood, bile, vitreous fluid, and urine values. No solid organs were obtained in any of the cases. Quantitations were performed using both an analytical standard and a fluvoxamine tablet for the preparation of calibrators. A comparison of quantitative values was made to evaluate the feasibility of using a tablet as the drug source for the preparation of calibrators when a pure reference material is unavailable. Postmortem peripheral blood concentrations ranged from approximately 0.5 mg/L in a case of suicidal shooting to approximately 6 mg/L in a case of drug overdose. Evidence of postmortem redistribution was noted in the only case for which both central and peripheral blood were obtained. Quantitations using an extracted drug tablet for the preparation of calibrators correlated well with quantitations using a pure reference material.     

Zolpidem distribution in postmortem cases

Zolpidem is the prototype of a class of sedative hypnotic drugs that are derivatives of imidazopyridine and is sold in the United States under the trade name Ambien. Over a four-year period, zolpidem was identified in eight cases investigated by the Office of the Chief Medical Examiner, State of Maryland. Zolpidem was identified by gas chromatography-nitrogen-phosphorus detection (GC-NPD) following an alkaline extraction and was confirmed by full-scan electron impact gas chromatography/mass spectrometry. Zolpidem was quantitated by GC-NPD in all specimens received. Five of the cases presented were deaths due to drug intoxication. In three of these cases, zolpidem was an incidental finding because the drug fatalities resulted from other drugs. In the other two cases of drug intoxication, zolpidem was present in elevated concentrations and was a contributing, but not exclusive cause of the drug intoxication. The remaining three cases were deaths that were not caused by drugs. The blood zolpidem concentrations in these cases were therapeutic (0.28, 0.12 and 0.19 mg/L, respectively). In six of the eight cases where both blood and urine were analyzed, the blood concentration was higher than the urine concentration. The distribution of zolpidem into the liver and kidney failed to identify any sequestration of the drug into either specimen.     

Markers of chronic alcohol use in hair: comparison of ethyl glucuronide and cocaethylene in cocaine users

Two direct ethanol metabolites, namely ethyl glucuronide (EtG) and cocaethylene (CE), in the hair of cocaine (COC) users were compared in this study. Hair samples (n=68) were submitted to the determination of EtG (by liquid chromatography-electrospray-tandem mass spectrometry) and of COC and metabolites, including CE (by gas chromatography-mass spectrometry). Quantitative and qualitative results were compared. No quantitative correlation was found between EtG and CE, as well as between EtG and the cocaethylene concentration divided by the concentration of COC and its metabolites (benzoylecgonine and ecgonine methylester, as COC equivalents). Nevertheless, many factors are supposed to affect the amount of the two substances incorporated in the hair matrix, such as the subject's habits in ethanol and COC use, genetic variability in the metabolism of both substances, and the different chemical and physical properties of EtG and CE. When establishing a cut-off of 4 pg/mg for EtG and of 200 pg/mg for CE, 47 samples tested positive for EtG and 41 samples tested positive for CE; 12 samples out of the 47 EtG-positives tested negative for CE (25%), whereas 6 samples out of the 41 CE-positives tested negative for EtG (15%). According to these data, EtG appears to be a more sensitive and specific marker of non-moderate alcohol users than CE.     

The interpretation of cocaine and benzoylecgonine concentrations in postmortem cases.

This study examined cocaine and benzoylecgonine concentrations in 100 consecutive deaths where either compound was identified in blood or urine specimens to determine whether any relationship between these concentrations and cause of death can be found. Forty-seven of the 100 cases were deaths attributed to cocaine, narcotic or combined cocaine and narcotic intoxication. There were 13 cases of cocaine intoxication where no psychoactive substance other than ethanol was detected. The mean cocaine concentration in these deaths was 908 ng/ml; three cases had cocaine concentrations greater than 2000 ng/ml, while the other ten cases had cocaine concentrations less than or equal to 700 ng/ml. The mean cocaine concentration in non-cocaine deaths where no psychoactive substance other than ethanol was detected was 146 ng/ml. This difference was not statistically significant. However, the average blood benzoylecgonine concentration in the 13 cocaine deaths was significantly higher than in the 19 non-cocaine deaths. A review of combined cocaine and narcotic deaths suggest that the narcotic is the main causative agent in these deaths.     

甲胺磷在犬体内的死后分布

目的建立甲胺磷的犬灌胃染毒致死模型,观察甲胺磷在犬体内的死后分布规律。方法犬经8倍LD50（7.4mg/kg）剂量甲胺磷灌胃后,观察其中毒症状,死亡后即刻解剖,分别取心、肝、脾、肺、肾、脑、右上肢肌、右下肢肌、胸肌、胃组织、心血、胆汁、玻璃体液和尿液,GC/MS和GC法检测其中甲胺磷含量。结果犬8倍LD50甲胺磷灌胃染毒后20min内出现中毒症状（,53.3±14.1）min死亡。各组织脏器及体液中甲胺磷含量由高到低分别为胃（99.84±0.87）μg/g、脾（46.87±28.67）μg/g、肝（43.82±22.74）μg/g、肾（43.79±29.04）μg/g、心血（35.36±13.98）μg/mL、肺（35.25±18.59）μg/g、尿34.81μg/mL、胸肌（19.23±17.18）μg/g、右上肢（16.92±8.98）μg/g、心（15.09±6.11）μg/g、右下肢（12.83±7.63）μg/g、脑（10.91±4.13）μg/g、胆汁（6.75±1.45）μg/mL、玻璃体液（6.22±4.97）μg/mL。结论甲胺磷在犬体内死后分布不均,胃、脾、肝、肾、心血、肺、尿检材中含量较高,可作为疑似甲胺磷中毒毒物分析的检材。     

Cocaine-induced psychosis and sudden death in recreational cocaine users

Fatal cocaine intoxication presenting as an excited delirium is described in seven recreational cocaine users. Symptoms began with the acute onset of an intense paranoia, followed by bizarre and violent behavior necessitating forcible restraint. The symptoms were frequently accompanied by unexpected strength and hyperthermia. Fatal respiratory collapse occurred suddenly and without warning, generally within a few minutes to an hour after the victim was restrained. Five of the seven died while in police custody. Blood concentration of cocaine averaged 0.6 mg/L, about ten times lower than that seen in fatal cocaine overdoses. Police, rescue personnel, and emergency room physicians should be aware that excited delirium may be the result of a potentially fatal cocaine intoxication; its appearance should prompt immediate transport of the victim to a medical facility. Continuous monitoring, administration of appropriate cocaine antagonists, and respiratory support will hopefully avert a fatal outcome.     

Levels of cocaine and its metabolites in washed hair of demonstrated cocaine users and workplace subjects

In a study of subjects in drug rehabilitation programs, cocaine and cocaine metabolite levels were determined in the hair of 75 subjects who had produced cocaine-positive urine results. The hair was analyzed after being washed with the 3.75 h wash procedure developed by this laboratory. In addition, results of testing 73 non-users are presented, as well as levels of cocaine, benzoylecgonine (BE), cocaethylene, and norcocaine from workplace population samples. The data support a recommendation of reporting as positive a sample with cocaine of 500 pg/mg hair and either a 5% ratio of benzoylecgonine (BE) to cocaine in samples, or the presence of cocaethylene at 50 pg/mg hair, or norcocaine at 50 pg/mg hair for samples < or =2000 pg cocaine/mg hair. For samples with cocaine present at >2000 pg/mg hair, the data indicate that a ratio of 5% BE may be an overly conservative approach. In appropriately washed hair samples, cocaine users can produce hair levels of <5% BE and thus a minimum BE cutoff in lieu of a ratio could be considered.     

曲马多在家兔体内的死后分布研究

目的研究曲马多在中毒家兔体内死后分布规律,为曲马多中毒检材采取提供实验依据。方法家兔经口给予10倍LD50曲马多,待家兔死亡后迅速解剖取样,气相色谱／质谱联用和气相色谱-FTD法测定其体液、脏器、大脑及右上肢和右下肢肌肉中曲马多的含量,比较其变化规律。结果血液和肝脏中曲马多的最低检出限分别为0．05μg/mL和0．05μg/g,提取回收率为97．60％±0．65％～103．10％±1．24％。曲马多在家兔体内的死后分布为：肾〉胃〉肝〉脾〉肺〉脑〉心〉上肢肌肉〉下肢肌肉〉〉体液（尿〉胆汁、心血〉玻璃体液）。结论大剂量曲马多中毒致死后在体内分布不均匀,组织中曲马多含量明显高于心血、胆汁等体液。     

Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.     

脑组织与法医学死亡时间推断

目前，通过脑组织推断死亡时间已经成为法医学领域研究的新热点，大量研究资料表明：死亡时间与脑组织细胞DNA、RNA、ATP含量及脑温度、脑组织血管内皮生长因子等变化有高度相关性。脑CT、MRI、磁共振波谱等检查手段对死亡时间的推断也有帮助。本文对国内外相关文献进行综述，以期为相关研究提供参考。     

Correlation of the incidence of cocaine and cocaethylene in hair and postmortem biologic samples

Hair samples are useful as a matrix for drug testing because drugs can be detected in hair for longer periods than in blood or urine. The authors report a prospective comparison of the detection of cocaine and cocaethylene in routine postmortem biologic specimens to the detection of cocaine and cocaethylene in hair. The authors collected hair samples from various areas of the head in 53 autopsy cases, prepared them, and analyzed them by gas chromatography/mass spectrometry (GC/MS) for cocaine and cocaethylene. The authors compared the results of hair analysis with the results of toxicologic analysis performed on routine postmortem samples by enzyme multiplied immunoassay technique and GC/MS. Cocaine was found in either biologic fluids or in hair in 16 of 53 samples tested. Nine samples were positive for cocaine in both biologic fluids and hair. Five samples contained cocaine only in biologic fluids, and two contained cocaine only in hair. Cocaethylene was present in two cases. Drug screening of hair provides additional information in some autopsy cases, but the authors have not made hair analysis a routine practice. It may prove useful to save hair samples in all cases for later analysis if warranted by additional history or autopsy findings.     

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。     

甲氰菊酯在家兔体内的死后分布研究

目的建立甲氰菊酯家兔灌胃染毒致死模型和生物检材中甲氰菊酯的气相色谱和气相色谱-质谱联用检测方法,研究甲氰菊酯在家兔体内的死后分布规律。方法家兔6只,甲氰菊酯经口灌胃染毒,死亡后迅速解剖,取心血、外周血、肝等组织,气相色谱和气相色谱-质谱联用法检测甲氰菊酯含量;部分组织经甲醛固定,HE染色,光镜观察其病理改变。结果家兔染毒后2～3h出现中毒表现,染毒后4.5～8h死亡。气相色谱和气相色谱-质谱联用法均检测到甲氰菊酯。甲氰菊酯在家兔体内死后分布为胃壁（458.92±32.82）μg/g、肾（46.47±6.30）μg/g、肝（35.79±20.11）μg/g、大脑（28.77±10.52）μg/g、心（26.49±4.10）μg/g、脾（22.23±5.37）μg/g、胆汁（10.87±1.42）μg/mL、肺（10.32±0.78）μg/g、周围血（8.14±1.12）μg/mL和心血（8.20±1.83）μg/mL。结论甲氰菊酯的灌胃染毒致死模型、气相色谱和气相色谱-质谱联用检测方法及死后分布规律可应用于甲氰菊酯中毒死亡案件的法医学鉴定及法医毒物动力学研究。     

The distribution of ethanol in postmortem blood specimens.

Ethanol was determined by gas chromatography in a variety of tissues and body fluids secured at autopsy in 61 cases. The specimens tested included right and left heart blood, femoral blood, pericardial fluid, cerebrospinal fluid, vitreous humor, urine, stomach contents, and brain. Statistical analysis of the cases revealed no significant differences among the various blood sites tested. However, the variations in blood ethanol concentrations among the various sampling sites within each case were as follows: 40 cases showed differences of less than 25%; 16 cases revealed variability between 25% and 50%, 4 cases had differences exceeding 50%. In one case, satisfactory blood analyses could not be accomplished. The larger variances occurred especially in those instances in which stomach alcohol concentration was 0.50% or greater. In one case, the variability amongst the different blood sites exceeded 400% (femoral blood--0.043%, right atrium--0.070%, root of aorta--0.156%); the brain was 0.050%, and the stomach contents was 1.2%. For all 61 cases, variances in blood alcohol content among the different sampling sites in a single cadaver ranged from 1.8 to 428%.     

大鼠百草枯中毒后体内的分布研究

目的建立生物检材中百草枯的超高效液相色谱-质谱联用检测方法,研究百草枯灌胃染毒致死的大鼠动物模型。方法大鼠以1/2 LD_(50)剂量灌胃染毒,分别于染毒后0.5h、2h、4h、8h、12h、24h、48h、72h处死解剖,采集心、肝、脾、肺、肾、脑、肌肉、膀胱和胃组织,UPLC-MS/MS法定量检测各组织中百草枯。结果试验中大鼠灌胃后,4h以内胃是主要分布器官,胃中含量最多,其他器官中含量相对较低。4h内除胃以外的脏器含量变化不大,4h后胃内百草枯含量有所下降,除胃以外的脏器含量均升高。各组织与脑组织比较具有显著性差异(P0.05)。结论百草枯在大鼠体内死后分布不均匀并且各组织含量随着时间变化有所改变。百草枯UPLC-MS/MS方法、口服染毒致死的动物模型、各组织分布规律可为甲百草枯中毒死亡案件提供检测依据。     

脑组织与其相关分析推断死亡时间的研究进展

推断死后间隔时间(postmortem interval,PMI)一直是法医学鉴定中需要解决的重要问题之一.可用于推断PMI的尸体检材有很多种,脑组织因其独特的解剖学位置与生理功能,是推断PMI的重要检材之一.本文从三个方面将根据脑组织推断PMI的方法进行综述,包括了通过脑组织的温度、形态特点等尸体现象推断PMI;通过...