Investigation of Postmortem Absorption and Redistribution After the Application of a Fentanyl Patch

Fentanyl deaths have increased with availability of transdermal patches. Interpretation of postmortem fentanyl levels may be complicated by postmortem redistribution and absorption of fentanyl from a patch. We applied an unused 100‐μg/h fentanyl patch onto the lower abdomen of a decedent with no premortem fentanyl exposure. Ocular fluid, blood, and urine were collected prior to placement, and the decedent was refrigerated for 23 h. Prior to the autopsy, urine, subcutaneous tissue under the patch, and samples from the same anatomic sites were obtained. We observed no fentanyl in any postpatch placement samples (LOD: 0.1 ng/mL for blood and vitreous fluid, 1.0 ng/mL urine, 2.0 ng/g for tissues). Although we observed no postmortem absorption of fentanyl, this was only a single case; therefore, we recommend that patches be removed after receipt of a cadaver before initiation of an autopsy, with the location of removed patch documented.     

Atropine Eye Drops: An Unusual Homicidal Poisoning

In March 2009, the body of a 51‐year‐old man was found in the boot of his car. The body had been frozen before being dismembered at the abdomen. The autopsy failed to determine the cause of death. Systematic toxicological analyses of the victim's peripheral blood and urine showed the presence of atropine, a powerful anticholinergic. Atropine was therefore specifically detected and quantified throughout the victim's biologic samples by HPLC‐MS² in the biologic fluids and UHPLC‐MS² in the hair. The atropine concentrations were 887 ng/mL in the cardiac blood, 489 ng/mL in the peripheral blood, 6693 ng/mL in the gastric contents (1.1 μg), 6753 ng/mL in the urine, and 2290 pg/mg in the hair. The blood concentrations measured in the decedent were consistent with an overdose of atropine, which was determined as the cause of death. The manner of death was a homicide with criminal intent.     

Fatal Intoxication with Methoxetamine

Methoxetamine (MXE) is a new synthetic drug of abuse structurally related to ketamine and phencyclidine. A case of a 29-year-old male with acute toxicity related to the analytically confirmed use of MXE is reported. The man was found dead at his residence. Biological material was analyzed using liquid chromatography–tandem mass spectrometry. The concentration of MXE in urine of the deceased was 85 μg/mL. Despite the vial containing the blood sample being destroyed during transportation and the blood leaking out into the cardboard packaging, the blood level of MXE was estimated. After determination of the cardboard grammage (approx. 400 g/m³) and the mean mass of the blood obtained after drying (0.1785 ± 0.0173 g per 1 mL), the estimated blood concentration of MXE was found to be 5.8 μg/mL. The high concentration of MXE in blood and urine and the circumstances of the case indicate an unintentional, fatal intoxication with this substance.     

Determination of Acetamiprid and IM‐1‐2 in PostMortem Human Blood,Liver, Stomach Contents by HPLC‐DAD

An HPLC‐DAD method was developed to detect and quantify a neonicotinoid insecticide acetamiprid (ATP) and its metabolite IM‐1‐2 in autopsy samples of a fatal intoxication case. The postmortem blood and tissue distribution of ATP and IM‐1‐2 was determined for the first time. The method showed acceptable precisions and recoveries with relative standard deviations of <10% for ATP level and 1.38 % for IM‐1‐2. The detection and quantification limits for ATP were 0.015 μg/mL and 0.030 μg/mL for blood and were 0.035 μg/g and 0.050 μg/g for liver samples, respectively. The mean contents of ATP were 0.79 μg/g in the liver, 47.35 μg/g in the stomach contents and 2.7 μg/mL in the blood. IM‐1‐2 content was 17.0 μg/g in the stomach contents. ATP and IM‐1‐2 were not detected in the urine. The presence of ATP and IM‐1‐2 in the samples was confirmed by GC‐MS. The method can be exploited in future forensic casework.     

Fatal Acute Poisoning from Massive Inhalation of Gasoline Vapors: Case Report and Comparison with Similar Cases

We describe a case of an acute lethal poisoning with hydrocarbons resulting from massive accidental inhalation of gasoline vapors. The victim, a 50‐year‐old man was found unconscious inside a control room for the transport of unleaded fuel. Complete autopsy was performed and showed evidence of congestion and edema of the lungs. Toxicological investigation was therefore fundamental to confirm exposure to fumes of gasoline. Both venous and arterial blood showed high values of volatiles in particular for benzene (39.0 and 30.4 μg/mL, respectively), toluene (23.7 and 20.4 μg/mL), and xylene isomers (29.8 and 19.3 μg/mL). The relatively low values found in the lungs are consistent with the fact that the subject, during the rescue, underwent orotracheal intubation followed by resuscitation techniques, while the low concentrations for all substances found in urine and kidneys could point to a death that occurred in a very short time after first contact with the fumes of gasoline.     

Α Simple Method for the Determination of Lacosamide in Blood by GC-MS

Lacosamide is a functionalized amino acid with antiepileptic function. Therapeutic drug monitoring (TDM) in patients for lacosamide is critical as it allows clinicians to control epileptic seizures. A single liquid–liquid extraction step was applied for the extraction of lacosamide from whole blood samples which were thereafter analyzed by GC-MS. Optimum extraction conditions were selected on the basis of experiments with various solvents at different pHs, indicating ethyl acetate at pH 12 as the most efficient parameters for the extraction of lacosamide. Method exhibited linearity from 2 to 100 μg/mL with R² = 0.998. Accuracy and precision were evaluated at three concentrations and found to be within acceptable limits. LOD and LOQ were determined at 0.1 and 0.5 μg/mL, respectively. Lacosamide was found to be stable at storage conditions. The developed method was applied successfully in clinical samples and postmortem blood sample from an overdose case.     

Vitreous Fluid and/or Urine Glucose Concentrations in 1335 Civil Aviation Accident Pilot Fatalities*

Abstract: During aviation accident investigations, vitreous fluid and urine samples from pilot fatalities are analyzed for glucose and blood for hemoglobin A_1c (HbA_1c) to monitor diabetic pilots and to discover other pilots with undiagnosed/unreported diabetes. The prevalence of elevated glucose concentrations in fatally injured pilots was evaluated by searching the Civil Aerospace Medical Institute’s Toxicology Database for the period 1998–2005. Out of 1335 pilots involving 363 vitreous fluid, 365 urine, and 607 vitreous fluid and urine analyses, 43 pilots had elevated glucose in vitreous fluid (>125 mg/dL) and/or in urine (>100 mg/dL). Of the 20 pilots whose blood samples were analyzed, nine had >6% HbA_1c—four were known diabetics, and five were unknown diabetics. Urinary glucose levels were elevated in all 13 known hyperglycemic pilots. A considerable number of pilots (30 of 43) had elevated glucose and HbA_1c (5 of 20), suggesting undiagnosed/unreported diabetic conditions.     

Distribution of dimethoate in the body after a fatal organphosphateintoxication

Many organophosphate pesticides (OPs) such as dimethoate are used to eradicate household pests, and those occurring in agriculture and forestry sectors. Combinations of two or more different insecticides have been manufactured to increase their effectiveness. A case of death is presented as suspected organophosphates intoxication. Autopsy was unremarkable except for grayish fluid in the stomach, with garlicky odor. A systematic toxicological analysis on post-mortem specimens revealed high concentrations of dimethoate in blood 38 μg/mL, urine 0.47 μg/mL, brain 2.2 μg/g, myocardial muscle 7.6 μg/g, liver 4.6 μg/g, lung 7.6 μg/g, skeletal muscle 21 μg/g, kidney 55 μg/g and gall bladder 31 μg/g. Blood alcohol was 2.85 g/L, cyclohexanone and cyclohexanol were also detected in the blood but not quantified. The cause of death was determined as organophosphate intoxication.     

Fatal Case of a 27‐Year‐Old Male After Taking Iboga in Withdrawal Treatment: GC‐MS/MS Determination of Ibogaine and Ibogamine in Iboga Roots and Postmortem Biological Material

We report the case of a man who died twelve hours after ingesting powdered iboga root, commonly taken for its stimulant and hallucinogenic properties. Ibogaine and ibogamine were quantified in the powder ingested and the victim's body fluids by GC‐MS/MS after liquid–liquid extraction (Toxi‐tubes A^®). The concentrations of ibogaine measured in the blood samples taken at the scene and in the peripheral blood, urine, and gastric fluid samples taken during the autopsy were 0.65, 1.27, 1.7, and 53.5 μg/mL, while the iboga content in the powder was 7.2%. Moreover, systematic toxicological analyses of biological samples showed the presence of diazepam and methadone in therapeutic concentrations. Death was attributed to the ingestion of a substantial quantity of iboga in the context of simultaneous methadone and diazepam consumption.     

Homicidal Paraquat Poisoning

Paraquat poisoning usually results from suicide, occupational, or accidental exposure. Herein, we report a rare fatal case of homicidal paraquat poisoning. A 58‐year‐old man was poisoned by taking paraquat‐mixed medicine and wearing paraquat‐soaked underwear. In the absence of a history of paraquat exposure, the patient was misdiagnosed with pulmonary infection and scrotal dermatitis and died of respiratory failure 24 days after the initial exposure to paraquat. Ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) was applied to detect and quantify paraquat in postmortem specimens. The concentration of paraquat in postmortem specimens from high to low is lung (0.49 μg/g), brain (0.32 μg/g), kidney (0.24 μg/g), liver (0.20 μg/g), cardiac blood (0.11 μg/mL), and stomach wall (<LOQ). Identification of homicidal paraquat poisoning is not easy for a clinician or a forensic pathologist, it is important to consider the possibility of paraquat poisoning when patients suffer from rapidly aggravating pneumonia of unknown origin.     

Suicide by Self‐Administration of a Drug Mixture (Propofol,Midazolam, and Zolpidem) in an Anesthesiologist: The First Case Report in Italy

The authors report an unusual case of suicide of an anesthesiologist, in which the suicide manner and means depend upon the victim's occupation. This is the first case report published in Italy of a death involving propofol and other drugs. The anesthesiologist was found dead with an empty drip still inserted in the hand and another one near his body. Forensic and toxicological findings suggested that the cause of death was a respiratory depression due to a self‐administration of a rapidly infused lethal drug mixture. Analytical drug quantification was performed by gas chromatography‐mass spectrometry. Blood analysis revealed: zolpidem (0.86 μg/mL), propofol (0.30 μg/mL), midazolam (0.08 μg/mL), thiopental (0.03 μg/mL), and amitriptyline (0.07 μg/mL). Adipose tissue and hair analysis suggested a previous and repeated use of these drugs verifying the fact that in Italy recreational abuse of anesthetic and sedative agents in health care practitioners is becoming an increasing problem.     

A mixed-drug intoxication involving venlafaxine and verapamil

This case report describes the suicide of a 52-year-old woman whose cause of death was attributed to a mixed-drug intoxication involving venlafaxine and verapamil. Venlafaxine is prescribed for the treatment of depression and should be used with caution in patients with cardiovascular disease. Verapamil is a calcium channel blocker primarily used for treatment of cardiovascular disorders. The following drug concentrations were determined in postmortem fluids: verapamil--3.5 mg/L (femoral blood), 9.4 mg/L (subclavian blood), and 1.0 mg/L (vitreous fluid); norverapamil--1.0 mg/L (femoral blood), 2.1 mg/L (subclavian blood), and 0.20 mg/L (vitreous fluid); verapamil and norverapamil could not be detected in bile or urine due to the high levels of erythromycin present; venlafaxine--6.2 mg/L (femoral blood), 8.6 mg/L (subclavian blood), 5.3 mg/L (vitreous fluid), 54.0 mg/L (bile), and 72.3 mg/L (urine); and O-desmethylvenlafaxine--5.4 mg/L (femoral blood), 8.3 mg/L (subclavian blood), positive (vitreous fluid), 29.2 mg/L (bile), and 9.5 mg/L (urine). The cause of death was determined to be a mixed-drug intoxication resulting from an overdose of verapamil and venlafaxine. The manner of death was determined to be suicide.     

Postmortem Fluid Concentrations of Heroin Biomarkers and Their Metabolites

Only limited data exist concerning the utility of complementary specimens in heroin-related deaths. As such, this report employed a validated LC-MS-MS method to quantify 6-monoacetylmorphine (6-MAM), 6-acetylcodeine (6-AC), and their metabolites morphine and codeine in blood with (BN) and without preservative (B) and the additional unpreserved specimens of vitreous humor, urine, stomach contents, and bile from 20 postmortem cases in which heroin was the primary cause of death. The median concentration of 6-MAM in BN was 0.011 mg/L, B was 0.008 mg/L, urine was 0.186 mg/L, vitreous humor was 0.022 mg/L, stomach contents was 0.147 mg/L, and bile was 0.012 mg/L. Only one case was found to be positive for 6-AC in B (case 6, 0.002 mg/L), and the median concentration of 6-AC was 0.002 mg/L in BN, 0.012 mg/L in urine, 0.003 mg/L in vitreous humor, 0.057 mg/L in stomach contents, and 0.004 mg/L in bile. These findings present new information on the distribution of these analytes in complementary matrices and support their inclusion for accurately determining the role of heroin in opioid-related deaths.     

Deaths Involving Methylenedioxypyrovalerone (MDPV) in Upper East Tennessee

Two deaths involving 3, 4‐methylenedioxypyrovalerone (MDPV) are reported. MDPV is a synthetic cathinone stimulant found in “bath salts” with neurological and cardiovascular toxicity. Biological specimens were analyzed for MDPV by GC/MS and LC/MS. A White man was found dead with signs of nausea and vomiting after repeatedly abusing bath salts during a weekend binge. Femoral venous blood and urine had MDPV concentrations of 39 ng/mL and 760 ng/mL. The second fatality was a White man with a history of drug and bath salt abuse found dead at a scene in total disarray after exhibiting fits of anger and psychotic behavior. Femoral venous blood and urine had MDPV concentrations of 130 ng/mL and 3800 ng/mL. The blood and urine MDPV concentrations are within the reported recreational concentration ranges (blood 24–241 ng/mL and urine 34–3900 ng/mL). Both decedents’ deaths were attributed to relevant natural causes in a setting of MDPV abuse.     

Analysis of hair after contamination with blood containing cocaine and blood containing benzoylecgonine

In post-mortem work, blood is a potential source of external contamination of hair. The present study was carried out to investigate the amount of drug absorbed into hair which has been contaminated with blood containing either cocaine or BE. Solutions were prepared containing 0.05, 0.1, 0.2, 0.5 and 3.0 μg/mL of either cocaine or BE in human blood. Samples of approximately 3.2 g of drug-free hair were contaminated by soaking in the blood solutions for 5 min. They were then removed and left at room temperature. Approximately 0.5 g of hair was collected from each of the blood soaked hair samples at 6 h, 1, 2, 4 and 7 days after contamination. As each hair sample was collected it was shampoo-washed to prevent further drug absorption. Hair samples were analysed in triplicate using a fully validated method described previously. EME and cocaethylene were also measured in order to find out if cocaine or BE was breaking down to these compounds. Both cocaine and BE were absorbed into hair in significant concentrations when the concentration in the blood was 0.5 μg/mL or greater; cocaine was more readily absorbed than BE. Cocaine broke down to EME (<LOQ) at 0.5 μg/mL and to EME (>LOQ) and BE (<LOQ) at 3.0 μg/mL. When the blood concentration of cocaine was 0.5 μg/mL or less, there was no evidence of it breaking down to form BE. From the samples soaked in blood containing BE, there was no evidence of the BE breaking down. The absorption of drug into hair did not increase as the contamination period increased from 6 h to 7 days.     

家兔玻璃体和脑脊液中异烟肼的高效液相色谱分析

目的　建立玻璃体和脑脊液中异烟肼的高效液相色谱分析方法。方法　以香草醛为衍生化试剂 ,经柱前衍生为异烟肼 -香草醛腙 ,直接对体液样品中的腙进行定性、定量分析 ,并以空白兔体液添加标准异烟肼对样品的前处理方法、仪器条件、线性范围、精密度、回收率进行全面考查后 ,测定急性染毒家兔玻璃体和脑脊液中的异烟肼浓度。结果　用上述方法分析兔玻璃体和脑脊液中异烟肼 ,其线性范围为 0 2～ 12 0 μg/ml,检测限 0 2 μg/ml,日内、日间精度均小于 4 9% ,回收率均在 97 1%以上。异烟肼在急性染毒家兔玻璃体中的浓度为 74 60± 7 40 μg/ml;脑脊液中为 88 95± 10 12 μg/ml。 结论　本文所建方法适用于异烟肼中毒者玻璃体和脑脊液中异烟肼的检测。     

A fatal case of oral ingestion of methanol. Distribution in postmortem tissues and fluids including pericardial fluid and vitreous humor.

A 41-year-old man ingested orally a large quantity of methanol and was found dead at home. The presence of methanol in body fluids and tissues was determined by head-space gas chromatography. The blood ethanol and acetone were negative. Tissue distribution of methanol showed that the kidney presented the highest content of methanol (5.13 g/kg) followed by liver (4.18 g/kg), vitreous humor (3.96 g/l), heart (3.45 g/kg), urine (3.43 g/l), pericardial fluid (3.29 g/l), blood (2.84 g/l) and finally stomach content (2.21 g/l).     

Simultaneous analysis of six amphetamines and analogues in hair, blood and urine by LC-ESI-MS/MS: Application to the determination of MDMA after low Ecstasy intake

A rapid and sensitive method using LC-MS/MS triple stage quadrupole for the determination of traces of amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”), 3,4-methylenedioxyethamphetamine (MDEA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair, blood and urine has been developed and validated. Chromatography was carried out on an Uptisphere ODB C₁₈ 5 μm, 2.1 mm × 150 mm column (Interchim, France) with a gradient of acetonitrile and formate 2 mM pH 3.0 buffer. Urine and blood were extracted with Toxitube A^® (Varian, France). Segmented scalp hair was treated by incubation 15 min at 80 °C in NaOH 1 M before liquid–liquid extraction with hexane/ethyl acetate (2/1, v/v). The limits of quantification (LOQ) in blood and urine were at 0.1 ng/mL for all analytes. In hair, LOQ was <5 pg/mg for MA, MDMA, MDEA and MBDB, at 14.7 pg/mg for AP and 15.7 pg/mg for MDA. Calibration curves were linear in the range 0.1–50 ng/mL in blood and urine; in the range 5–500 pg/mg for MA, MDMA, MDEA and MBDB, and 20–500 pg/mg for AP and MDA. Inter-day precisions were <13% for all analytes in all matrices. Accuracy was <20% in blood and urine at 1 and 50 ng/mL and <10% in hair at 20 and 250 pg/mg. This method was applied to the determination of MDMA in a forensic case of single administration of ecstasy to a 16-year-old female without her knowledge during a party. She suffered from hyperactivity, sweating and agitation. A first sample of urine was collected a few hours after (T + 12 h) and tested positive to amphetamines by immunoassay by a clinical laboratory. Blood and urine were sampled for forensic purposes at day 8 (D + 8) and scalp hair at day 60 (D + 60). No MDMA was detected in blood, but urine and hair were tested positive, respectively at 0.42 ng/mL and at 22 pg/mg in hair only in the segment corresponding to the period of the offence, while no MDA was detectable. This method allows the detection of MDMA up to 8 days in urine after single intake.