CI-mass fragmentographic analysis of methamphetamine and amphetamine in human autopsy tissues after acute methamphetamine poisoning

A 22-year-old male methamphetamine abuser was put under police protection owing to his abnormal state of excitation, but died 1 h later. Distribution of methamphetamine and amphetamine in the body was analyzed by the chemical ionization mass fragmentographic method. Amphetamine/methamphetamine concentrations (μmol/100 g) were $\text{0.24}\text{5.59}$ in blood, $\text{0.41}\text{9.43}$ in liver, $\text{0.41}\text{10.02}$ in brain, $\text{0.37}\text{9.80}$ in kidney, $\text{0.18}\text{4.57}$ in muscle, $\text{0.02}\text{0.63}$ in subcutaneous fat and $\text{1.87}\text{1464}$ in gastric contents. Total amount of methamphetamine hydrochloride in stomach contents was about 54 mg. Amphetamine concentrations in tissues ranged from 3.2% to 4.3% of methamphetamine, and was 0.1% in stomach contents. Amphetamine in tissues seems to be a metabolite of methamphetamine, and amphetamine in gastric contents is presumed to result from gastric mucous excretion. The blood concentration of methamphetamine was at a fatal level, and the total amount of the drug in gastric contents indicates that fatal poisoning occurred by ingestion.     

Articles found in the possession of a methamphetamine abuser

A plastic syringe containing bloody fluid, 2 ampules of 20% glucose, an ampule containing diphenhydramine hydrochloride and calcium bromide, powder in a plastic bag and powder wrapped in paper were among the articles found in the possession of a 42-year-old male methamphetamine abuser, who had been taken to a mental hospital owing to his hallucinations.Examination of the patient revealed several recent needle punctures on the left forearm. The concentration of methamphetamine and its metabolite, amphetamine, in blood collected 1 day following the last intake was 76 nmol/100 g. Analysis of the powder and of the contents of the syringe revealed methamphetamine hydrochloride at a concentration of 99.0–99.5% and 7.4%, respectively. Neither glucose nor diphenhydramine were detected in the contents of the syringe.It would seem that the patient abused methamphetamine hydrochloride by intravenous injection after dissolving it in city water or distilled water.     

甲基苯丙胺在家兔体内的毒物代谢动力学研究

目的研究甲基苯丙胺及其代谢物苯丙胺在家兔体内的毒物代谢动力学行为。方法GC/MS法测定家兔灌胃甲基苯丙胺后不同时间点血、尿中甲基苯丙胺和代谢物苯丙胺浓度,采用3P97程序进行房室模型拟合以及毒物代谢动力学参数计算。结果甲基苯丙胺和苯丙胺在家兔体内的毒物代谢动力学过程均呈一级动力学特征,符合二室开放模型。甲基苯丙胺在家兔体内Cm ax为1.457 mg/L±0.094 mg/L,Tm ax为1.557h±0.078h,t1/2 ka、t1/2α和t1/2β分别为0.384h±0.052h、1.614h±0.036h和3.007h±0.430h,CL为1.769 L/h/kg±0.114 L/h/kg。甲基苯丙胺的毒物代谢动力学方程为:C t=2.767 e-0.746 t+1.454 e-0.234 t+4.119 e-1.746 t。结论甲基苯丙胺在家兔体内吸收、消除和代谢都较快。建立的甲基苯丙胺毒物代谢动力学方程和参数可为甲基苯丙胺分析的合理取样、从血药浓度推断服毒时间以及甲基苯丙胺滥用的法医学鉴定提供理论依据。     

Nails as useful materials for detection of methamphetamine or amphetamine abuse

Methamphetamine and amphetamine could be demonstrated in nail clippings obtained from methamphetamine users by sensitive gas chromatography/chemical ionization mass spectrometry with N-methylbenzylamine as an internal standard. The methamphetamine levels in fingernails were comparable to those in hair. Both stimulants were more concentrated in toenails than in fingernails. The detection of methamphetamine and amphetamine in nails provides an alternative informatian to that in hair on their past abuse.     

Distribution of methamphetamine and amphetamine in drug abusers’ head hair

In order to aid the interpretation of hair results from methamphetamine (MA) abusers the MA and amphetamine (AP) concentrations in 2070 hair samples were statistically evaluated. The MA and AP concentrations in hair were put into three groups arbitrarily representing low, medium and high ranges and the metabolite-to-parent drug ratios of each group were examined. The concentration ranges proposed here were also applied to the interpretation of five authentic cases. The low, medium and high ranges of MA were 0.5–4.2, 4.2–24.5 and 24.5–608.9 ng/mg and those of AP were 0.1–0.4, 0.4–1.7 and 1.7–41.4 ng/mg. The AP-to-MA ratios showed large variation but a tendency that it decreased as the MA ranges increased. This evaluation was very useful to presume the severity of individuals’ MA abuse and to provide law enforcement agencies more understandable information. It could also facilitate the court's decision regarding specific circumstances surrounding the drug-related crimes.     

A fatal poisoning with LSD

Radioimmunoassay, high-performance liquid chromatography and capillary gas chromatography-mass spectrometry were used to detect and measure LSD in the first reported case of fatal poisoning by LSD. The levels found in ante-mortem serum and plasma and in post-mortem blood, liver blood and stomach contents are given.     

A fatal doxepin poisoning associated with a defective CYP2D6 genotype

It has been suggested that the polymorphism of the CYP2D6 gene can contribute to occurrence of fatal adverse effects. We therefore investigated postmortem toxicology cases of fatal drug poisonings related to CYP2D6 substrates, with the manner of death denoted as accidental or undetermined. CYP2D6 genotypes were determined in 11 consecutive cases with samples available for DNA analysis. A case of fatal doxepin poisoning with an undetermined manner of death was found to coincide with a completely nonfunctional CYP2D6 genotype (*3/*4), indicating a total absence of CYP2D6 enzyme and suggesting a poor metabolizer phenotype. The doxepin concentration was 2.4 mg/L, the concentration of nordoxepin 2.9 mg/L, and the doxepin/nordoxepin ratio 0.83, the lowest found among the 35 nordoxepin-positive postmortem cases analyzed during the same year. No alcohols or other drugs were detected in the case. The CYP2C19 genotype was determined as that of an extensive metabolizer. The high N-desmethylmetabolite concentration is not consistent with acute intoxication. It is therefore probable that the defective genotype has contributed to the death, possibly involving repeated high dosage of doxepin. Our case strongly emphasizes that a pharmacogenetic analysis in postmortem forensic setting may reveal new insight to the cause or manner of death.     

A fatal case of poisoning with cantharidin.

A case of fatal poisoning due to voluntary ingestion of cantharides powder for aphrodisiac purposes is reported. Clinical history, autopsy and analytical findings are described. Blood and urine samples collected during the 30 h of survival, as well as the cantharides product, were analyzed by gas chromatography-mass spectrometry. On the basis of the percentage of the active principle measured in the powder, an ingested dose of 26-45 mg of cantharidin could be estimated.     

A fatal poisoning with 5-methoxy-N,N-diisopropyltryptamine, Foxy

A fatal overdose involving case by 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is reported. 5-MeO-DIPT and its two metabolites, 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N-isopropyltryptamine (5-MeO-NIPT), were identified by LC-MS. The level of 5-MeO-DIPT, 5-OH-DIPT and 5-MeO-NIPT in blood and urine was 0.412, 0.327 and 0.020 microg/ml, and 1.67, 27.0 and 0.32 microg/ml, respectively. These blood and urine levels were higher than published data for such poisoning.     

A high selective screening test for methamphetamine in human urine

A high selective screening test (Ad-Tip method) for methamphetamine in human urine has been devised. The method involves a brief extraction from a urine sample with an Ad-Tip (ODS-silica minicolumn), washing, eluting with modified Simon's reagent, and coloration with carbonate buffer. Detection limit of methamphetamine in urine is 1 microgram/ml and the test takes within 3 min/sample. The results of the Ad-Tip method were almost identical to those of laboratory analyses.     

A case of fatal aconitine poisoning by Monkshood ingestion

Accidental aconitine poisoning is extremely rare in North America. This report describes the confirmation of a case of accidental aconitine poisoning using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The case involved a 25-year-old man who died suddenly following a recreational outing with friends where he consumed a number of wild berries and plants including one that was later identified as Monkshood (Aconitum napellus). Postmortem blood and urine samples were available for analysis. All routine urine and blood toxicology screens were negative. The LC-MS/MS method allowed sensitive quantification of aconitine, the main toxin in A. napellus, and showed 3.6 and 149 microg/L in blood and urine, respectively. These concentrations were similar to that reported in other aconitine-related deaths. This case illustrates the dangers of consuming unidentified plants, and documents concentrations of aconitine in blood and urine in a fatal case of A. napallus-related poisoning.     

A fatal dichlorvos poisoning: concentrations in biological specimens

Abstract:  A 54-year-old man was found dead with a bottle containing a brownish fluid near him. A toxicological screening was carried out in blood, urine, and stomach content. Only dichlorvos (2,2 dichlorovinyl O-O dimethylphosphate or DDVP) was found. A simple and rapid method, using DDVP-D₆ as an internal standard, was developed for the determination of DDVP by gas chromatography/mass spectrometry (GC/MS). The method was linear from 1 to 10 mg/L. Intraday and interday precisions were all <15%. DDVP concentration in cardiac blood was approximately four times higher than in peripheral blood. A high concentration was found in the heart showing a cardiac tropism of DDVP, kidney and lung concentrations being much lower. No DDVP was found in liver. DDVP stomach content was 38 g. The amount presumed ingested was 82 g, c . 1000 mg/kg of body. The oral LD₅₀ for DDVP ranges between 20 and 1090 mg/kg in animals but is not known for humans.     

A fatal complication of a vena caval filter associated with pulmonary thromboembolism

Vena caval filters are increasingly used for the prevention of pulmonary thromboembolism in patients with deep vein thrombosis ever since the introduction of the stainless steel Greenfield filter in the 1970s. Although complications associated with their use are rare, they can be fatal, and therefore it is important for forensic pathologists to be aware of their occurrence. Because of the ramifications of a medical device failure, a thorough documentation of the autopsy findings is essential. We describe an unusual case of a 75-year-old woman who developed a fatal pulmonary thromboembolism with concurrent migration of a lesser known type of vena caval filter to the right ventricle occurring 19 days after filter placement. A review of the types of vena caval filters in current use, and their complications, are discussed.     

A case of fatal poisoning with the aconite plant: quantitative analysis in biological fluid.

In recent years recorded cases of plant poisoning have become rare, this may in part be due to the possibility of plant ingestion not being indicated at the beginning of an investigation. Aconitum napellus (aconite, Wolfsbane, Monkshood) is one of the most poisonous plants in the UK. It contains various potent alkaloids such as aconitine, isoaconitine, lycaconitine and napelline. Ingestion of Aconitum plant extracts can result in severe, potentially fatal toxic effects. This paper describes the analytical findings in a recent death in the UK. resulting from deliberate ingestion of Aconitum napellus extract. The concentrations of aconitine measured by HPLC-DAD in the post mortem femoral blood and urine were 10.8 micrograms/L and 264 micrograms/L, respectively. The aconitine concentration in the ante mortem urine was 334 micrograms/L and was estimated to be 6 micrograms/L in the ante mortem serum. Hence, accidental, suicidal or homicidal poisoning due to the ingestion of plant material remains a possibility and should be borne in mind when investigating sudden or unexplained death.     

A fatal case of hypothermia associated with hemorrhages of the pectoralis minor, intercostal, and iliopsoas muscles

In a morning in January, a male in his early sixties was found dead in an outdoor parking area. The minimum temperature during the night before he was found dead was estimated to be 4.0 degrees C. Autopsy revealed the pinkness of hypostasis, slight abrasions and bruises on the face and the extremities, collapse of the lungs, and slight gastric submucosal hemorrhage. Histologic examination revealed compact arrangement of cardiac muscle fibers and cytoplasmic vacuolation in the adenohypophysis. Toxicologic examination demonstrated hyperacetonemia (51.2 microg/mL). Ubiquitin, one of the stress proteins that are induced by several stimuli, including severe cold, was detected in several organs. We concluded that the cause of his death was lethal hypothermia. In addition, hemorrhages were observed in the subfascial and/or intramuscular parts of the pectoralis minor, first intercostal, and iliopsoas muscles. Although it has been reported that iliopsoas muscle hemorrhage can result from hypothermia, there have been few reports concerning hypothermia-associated hemorrhages of the pectoralis minor and/or intercostal muscles. We presumed that intense shivering and/or effort ventilation during the course of lethal hypothermia might cause these muscle hemorrhages.     

A fatal case of suspected anaphylaxis with cefoperazone and sulbactam: LC-MS analysis

Cefoperazone and sulbactam are prescribed in combination and used in the treatment of moderate to severe bacterial infections. Serious anaphylaxis is a rare side effect. This report describes a fatal case of suspected anaphylaxis after intravenous administration of a combination of the two drugs. Heart blood was analyzed for cefoperazone by protein precipitation with acetonitrile and by liquid-liquid precipitation for sulbactam after protein precipitation with aqueous acetonitrile, followed by tandem mass spectrometry in the product ion scan mode for identification and by liquid chromatography mass spectrometry in the selected ion monitoring mode for quantitation. Calibration curves for cefoperazone and sulbactam were linear over the range 0.07 to 1.93 and 0.046 to 0.914 microg/ml respectively. The decedent's blood concentrations of cefoperazone and sulbactam were 0.368 and 0.143 microg/ml respectively. As these concentrations were below concentrations reported after single dosing studies and below those considered to be minimally inhibitory, death was presumed to have been caused by hypersensitivity and not an overdose. In conclusion, this procedure is useful for detecting and quantitating cefoperazone and sulbactam in postmortem blood and may be useful in the evaluation of anaphylaxis.     

Diesel fumes do kill: a case of fatal carbon monoxide poisoning directly attributed to diesel fuel exhaust with a 10-year retrospective case and literature review*

While it is known that diesel fuel combustion engines produce much lower concentrations of carbon monoxide (CO) than gasoline engines, these emissions could certainly generate lethal ambient concentrations given a sufficient amount of time in an enclosed space and under suitable environmental conditions. The authors report a case of CO poisoning which was initially referred for autopsy as a presumed natural death of a truck driver found in the secure cab of a running diesel tractor trailer truck. Completion of the preliminary investigation ascribed death to complications of ischemic heart disease (IHD), pending toxicological analysis that included quantification of CO. When the toxicology results showed lethal blood COHbg, the cause of death was re-certified as CO intoxication secondary to inhalation of (diesel) vehicular exhaust fumes. Because of the unique source of fatal CO intoxication in this case, the contributory IHD and the possible contaminants in the putrefied blood, a 10-year retrospective review was conducted on all nonfire related CO deaths autopsied (n = 94) at the Office of the Chief Medical Examiner in Louisville, KY from 1994 to 2003. For validation of the COHbg detection method used by the Kentucky Office of Forensic Toxicology (KYOFT), blood samples from these cases along with controls were submitted to three laboratories using various analytical methods yielding no statistically significant differences. Lastly, an extensive literature review produced no scientifically reported cases of fatal CO poisoning attributed to diesel fuel exhaust.     

Animal-related fatalities--part II: characteristic autopsy findings and variable causes of death associated with envenomation, poisoning, anaphylaxis, asphyxiation, and sepsis

In addition to blunt and sharp trauma, animal-related fatalities may result from envenomation, poisoning, anaphylaxis, asphyxiation, and sepsis. Although the majority of envenomation deaths are caused by hornets, bees, and wasps, the mechanism of death is most often anaphylaxis. Envenomation resulting from the injection of a poison or toxin into a victim occurs with snakes, spiders, and scorpions on land. Marine animal envenomation may result from stings and bites from jellyfish, octopus, stonefish, cone fish, stingrays, and sea snakes. At autopsy, the findings may be extremely subtle, and so a history of exposure is required. Poisoning may also occur from ingesting certain fish, with three main forms of neurotoxin poisoning involving ciguatera, tetrodotoxin ingestion, and paralytic shellfish poisoning. Asphyxiation may follow upper airway occlusion or neck/chest compression by animals, and sepsis may follow bites. Autopsy analysis of cases requires extensive toxinological, toxicological, and biochemical analyses of body fluids.     

A longitudinal analysis of factors associated with reporting violent crimes to the police

The use of generalized estimating equations and time-series methods for fitting longitudinal models in the National Crime Victimization Survey (NCVS) is discussed, with reference to the relation between the reporting of a violent crime to the police and previous victimizations. Two longitudinal models are fit to NCVS data to predict the likelihood of reporting a violent crime to the police based on characteristics of the victim and the incident and based on previous victimization experiences. In both models, it is found that higher reporting rates are associated with positive results accruing from reporting previous victimization to the police.     

A cross-sectional study on expression of anger and factors associated with criminal recidivism in prisoners with prior offences

Objective: The purpose of this study is to determine demographical characteristics leading to crime recidivism and define anger levels and anger expression manners for those who re-commit crime.Method: All the literate inmates in zmit Closed Penitentiary were included in this cross-sectional study. The prisoners were asked to respond to State-Trait Anger Expression Inventory. Their socio-demographic data were collected and a questionnaire was given to them to determine their state of imprisonment, sentence, nature of the crime in which they were involved, their criminal history, their relationship with inmates and prison staff and substance and alcohol use.Results: Of the 438 prisoners, 302 (68.9%) responded to the questionnaires. Crime recidivism among the study cohort was observed to be 37.4%.Mean trait anger, anger out and anger in scores were significantly higher in prisoners with criminal recidivism in comparison with those who did not have prior criminal records. However, mean anger control scores for prisoners with or without criminal recidivism were similar. Unemployment, education level completed at secondary school or below, having committed a crime under the influence of alcohol or narcotics, having been involved in prison fights, having resisted police officers, caused damage in their vicinity when angry and violent crimes were all found to be possible causes of criminal recidivism. Educational level completed at secondary school or below, getting into fights with other prisoners, unemployment and resisting police officers were determined to be the strongest indicators to predict criminal recidivism when all variables were considered according to a logistic regression model.Conclusion: It can be proposed that those who have problems with officials or hostile towards others constitute a risk group for criminal recidivism. If prisoners with criminal recidivism can be helped to identify and control their anger, their risk of committing a new crime can be minimised.