2-Fluorodeschloroketamine consumption: About two deaths and a case of self-mutilation.

2-Fluorodeschloroketamine (2-FDCK) is a new psychoactive substance (NPS), close to the ketamine structure. Few cases of 2-FDCK intake are described in the forensic literature, especially concerning death cases. We report here a case of self-mutilation (Case 1) and two forensic deaths linked to 2-FDCK consumption. The second case involved a man found dead in the street, having been stabbed. The third case was a man found dead following a suspected overdose and in an advanced state of putrefaction. For all three cases, biological fluids such as blood and urine were analyzed, as was hair for the two fatal cases. The aim of this study was to identify and quantify 2-FDCK and its main metabolites in different matrices. Biological fluids and hair were analyzed by liquid chromatography coupled with tandem mass spectrometry after decontamination and extraction. Seized products were analyzed by gas chromatography-mass spectrometry and assayed, when possible, by ultra-performance liquid chromatography with diode-array detection. 2-FDCK was detected and quantified in the peripheral blood of Cases 1, 2 and 3 (457, 758 and 5885 µg/L, respectively), as were its main metabolites nor-2-FDCK, dihydro-nor-2-FDCK and dihydro-2-FDCK. In the 1 cm long hair of Cases 2 and 3, 2-FDCK was also detected (approximately 4149 and 79824 pg/mg, respectively). Deschloroketamine (DCK) was found in the biological fluids of Cases 1, 2 and 3 (10, 8 and 350 µg/L, respectively), as well as in hair of Cases 2 and 3 (65 and around 8119 pg/mg, respectively). In Case 3, as a small bag containing DCK powder was seized from his home, we can assume that DCK was taken. On the contrary, to our knowledge, it has not been established that Case 2 took DCK alone, so we can assume that it may be the first case to report DCK from 2-FDCK metabolism in fluids as well as in hair.

Exposure of the general French population to metals and metalloids in 2014-2016: Results from the Esteban study.

BACKGROUND: The purpose of the Esteban study was to describe levels of various biomarkers of exposure to several environmental pollutants, including metals and metalloids, among the French population. This paper describes the distribution of concentrations of 28 metals and metalloids in two different populations, and estimates the main determinants of exposure to total arsenic, the sum of inorganic arsenic (iAs) and its two metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), cadmium, chromium, copper, mercury and nickel. METHODS: Esteban is a cross-sectional study conducted between 2014 and 2016 on a random sample of 2503 adults (18-74 years old) and 1104 children (6-17 years old) from the general population. The data collected included biological samples (blood, hair, and urines), socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors and lifestyle. The geometric mean and percentiles of the distribution were estimated for each metal. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. RESULTS: Only four metals had a quantification rate below 90% in adults (beryllium, iridium, palladium, and platinum), and three metals in children (beryllium, iridium, and platinum). The concentrations of total arsenic, cadmium, chromium and mercury were higher than those found in most international studies. The determinants significantly associated with exposure were mainly diet and smoking. CONCLUSIONS: Esteban provided a nationwide description of 28 metal and metalloid exposure levels for adults (some never measured before) and for the first time in children. The study results highlighted widespread exposure to several metals and metalloids. These results could be used to advocate public health decisions for continued efforts to reduce harmful exposure to toxic metals. The Reference values (RV95) built from Esteban could also be used to support future government strategies.

Difficulties interpreting concentrations in fatal cases: example of 2,5-dimethoxy-4-chloroamphetamine.

PURPOSE: Death related to the use of drugs is evident when drugs are detected in biological matrices within toxic levels, but sometimes it can be less obvious. Intoxications after 2,5-dimethoxy-4-chloroamphetamine (DOC) use are occurring but up to date, only one fatality has been reported. Here we present the case of a young woman admitted to hospital as she presented vomiting, convulsions and cardiorespiratory arrest. METHODS: Blood ethanol concentration was determined using gas chromatography with flame ionization detection and toxicological screenings (blood, gastric content and hair samples) were performed using liquid chromatography with diode array detection, gas chromatography or liquid chromatography with mass spectrometry detection. RESULTS: Her health state declined with cardiac troubles, organs failure and cerebral edema till death occurring 4 days later. The autopsy revealed the presence of hemorrhagic infiltration inside the left ventricle, pulmonary edema and hemorrhagic infiltration of the terminal ileum. The analysis of biological fluids confirmed the presence of DOC (< 10 ng/mL in cardiac blood sample), buprenorphine, cocaine and cannabis metabolites. The analysis of hair highlighted a history of drugs abuse. CONCLUSION: In the absence of evident identified cause, the hypothesis of a death due to acute drugs use within a history of chronic consumption of drugs has been put forward. The concentration of some substances such as new psychoactive substances can be low in biological matrices but the toxic effects can be additive and lead to death even within young people, hence the importance of the knowledge of consumption history.

Commentary on current changes of the SoHT 2016 consensus on alcohol markers in hair and further background information.

The consensus on alcohol markers in hair was revised for the fourth time by an expert group of the Society of Hair Testing based on current state of research. This revision was adopted by the members of the Society during the business meeting in Brisbane on August 29th 2016. For both markers, ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs), two cut-off values for discrimination between teetotalers or occasional low amount consumption and moderate alcohol drinking (low cut-off), and between non-excessive (abstinence up to moderate alcohol intake) and chronic excessive drinking (high cut-off value) were critically examined. For the current revision, the cut-off values for EtG (7pg/mg and 30pg/mg, respectively) remained unchanged despite different findings or discussions published in the meantime. This was mainly due to the lack of broader data collections from new studies with great numbers of volunteers following thorough study concepts. In contrast, an essential change of the consensus was accepted for the FAEEs, where the concentration of ethyl palmitate (E16:0) can be used autonomously for interpretation instead of the concentration sum (ΣFAEE) of the four esters ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate, as previously applied. After evaluation of the data from seven laboratories, the E16:0 cut-off for abstinence assessment was defined at 0.12ng/mg for the 0-3cm segment and at 0.15ng/mg for the 0-6cm segment. The cut-off for chronic excessive drinking was fixed at 0.35ng/mg for the 0-3cm segment and at 0.45ng/mg for the 0-6cm segment. The use of E16:0 with these cut-offs in place of ΣFAEE for alcohol intake assessment produces only a minor loss in discrimination power, leads to no essential difference in the interpretation concerning chronic excessive alcohol consumption and is suitable to confirm EtG results in abstinence assessment if ethanol containing hair sprays or lotions are excluded.

Ocfentanil overdose fatality in the recreational drug scene.

This paper describes the first reported death involving ocfentanil, a potent synthetic opioid and structure analogue of fentanyl abused as a new psychoactive substance in the recreational drug scene. A 17-year-old man with a history of illegal substance abuse was found dead in his home after snorting a brown powder purchased over the internet with bitcoins. Acetaminophen, caffeine and ocfentanil were identified in the powder by gas chromatography mass spectrometry and reversed-phase liquid chromatography with diode array detector. Quantitation of ocfentanil in biological samples was performed using a target analysis based on liquid-liquid extraction and ultra performance liquid chromatography tandem mass spectrometry. In the femoral blood taken at the external body examination, the following concentrations were measured: ocfentanil 15.3µg/L, acetaminophen 45mg/L and caffeine 0.23mg/L. Tissues sampled at autopsy were analyzed to study the distribution of ocfentanil. The comprehensive systematic toxicological analysis on the post-mortem blood and tissue samples was negative for other compounds. Based on circumstantial evidence, autopsy findings and the results of the toxicological analysis, the medical examiner concluded that the cause of death was an acute intoxication with ocfentanil. The manner of death was assumed to be accidental after snorting the powder.

Synthetic phosphodiesterase-5-inhibitors use/abuse and interest of hair testing: reporting of a rape case.

If classic phosphodiesterase-5 (PDE-5) inhibitors are well known, new synthetic PDE-5 analogues are of more recent introduction. Some of them have already been tested in dietary supplements. We describe here a rape case following the consumption of pills bought on the Internet and containing new synthetic PDE-5 inhibitors. The assailant declared that he lost control after ingesting these pills for the first time. Analyses of conventional matrices (blood, urine) don't allow us to highlight the intake of any substances in relation to this offence due to late sampling (5 days after the offence). Therefore, we have developed an analytical approach to test for PDE-5 inhibitors in hair including the two new synthetic PDE-5 inhibitors analogues - thiosildenafil and hydroxythiohomosildenafil - previously identified in the pills. This new method was validated and applied to the hair samples of the victim and the suspect. Analyses were conducted using a liquid/liquid extraction followed by liquid chromatography coupled with a mass spectrometer in multiple reaction monitoring mode detection. The 2-centimetre proximal hair section of the suspect revealed the presence of thiosildenafil (48 pg/mg), hydroxythiohomosildenafil (24 pg/mg), and sildenafil (7.5 pg/mg). To our knowledge, it is the first time that these two new synthetic PDE-5 inhibitors were detected in biological samples and especially in hair. Complementary investigations showed that a single pill taken by a volunteer provided similar levels in thiosildenafil (35 pg/mg), hydroxythiohomosildenafil (17 pg/mg), and sildenafil (8 pg/mg) to those found in the previous case described here.

Interpretation of pharmaceutical drug concentrations in young children's head hair.

Three separate cases of child administration of prescription drugs are described. Following liquid-liquid extraction, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to identify and quantify methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenyl-1-pyrrolidine (EDDP), tramadol, amitriptyline, and nortriptyline in children's hair. The children's age ranged from 14 months to 7 years; in all three cases, the drug in question was detected in more than one section of hair. Methadone was detected in the concentration range of 0.65-0.99 and 0.04-0.4 ng/mg; tramadol was detected in the concentration range of 1.5-2.2 ng/mg; amitriptyline and nortriptyline were detected in the concentration range of 0.18-1.06 and 0.38-2.0 ng/mg, respectively. In each case, the children's parents admitted to or were found guilty of drug administration to the child. These cases demonstrate the added value of hair testing and emphasize the importance of using hair samples to complement conventional analyses.

Fatal accidental hydrogen sulfide poisoning: a domestic case.

Hydrogen sulfide (H(2)S) poisonings are classically reported in occupational settings. We describe an unusual domestic case of fatal acute poisoning by H(2)S inhalation. A mother and her infant daughter were found dead in the kitchen of their home. The emergency medical team described a strong smell of rotten eggs, suggesting acute H(2)S poisoning. Autopsies revealed only multiorgan congestion. H(2) S was measured in blood and lung tissue samples by gas chromatography/mass spectrometry. Body fluids were negative, but H(2) S was found in the lungs of both the mother and the child at concentrations of 1.46 and 1.92 mg/kg, respectively, concentrations described in the literature as potentially lethal. Expert surveys of the premises suggested a complex mechanism involving both defective maintenance of the pipes and drains of the building and faulty assembly of the sink siphon, which led to stagnation of waste water and formation of a pocket of H(2)S.

Urinary arsenic levels in the French adult population: the French National Nutrition and Health Study, 2006-2007.

The French Nutrition and Health Survey (ENNS) was conducted to describe dietary intakes, nutritional status, physical activity, and levels of various biomarkers for environmental chemicals (heavy metals and pesticides) in the French population (adults aged 18-74 years and children aged 3-17 years living in continental France in 2006-2007). The aim of this paper was to describe the distributions of total arsenic and the sum of iAs+MMA+DMA in the general adult population, and to present their main risk factors. In the arsenic study, 1500 and 1515 adults (requested to avoid seafood intake in the previous 3 days preceding urine collection) were included respectively for the analysis of the sum of inorganic arsenic (iAs) and its two metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and for the total arsenic. Results were presented as geometric means and selected percentiles of urinary arsenic concentrations (µg/L) and creatinine-adjusted urinary arsenic (µg/g of creatinine) for total arsenic, and the sum of inorganic arsenic and metabolites (iAs+MMA+DMA). The geometric mean concentration of the sum of iAs+MMA+DMA in the adult population living in France was 3.34 µg/g of creatinine [3.23-3.45] (3.75 µg/L [3.61-3.90]) with a 95th percentile of 8.9 µg/g of creatinine (10.68 µg/L). The geometric mean concentration of total arsenic was 11.96 µg/g of creatinine [11.41-12.53] (13.42 µg/L [12.77-14.09]) with a 95th percentile of 61.29 µg/g of creatinine (72.75 µg/L). Urinary concentrations of total arsenic and iAS+MMA+DMA were influenced by sociodemographic and economic factors, and by risk factors such as consumption of seafood products and of wine. In our study, covariate-adjusted geometric means demonstrated several slight differences, due to consumption of fish, shellfish/crustaceans or wine. This study provides the first reference value for arsenic in a representative sample of the French population not particularly exposed to high levels of arsenic (10 µg/g of creatinine). It shows that urinary arsenic concentrations in the French adult population (in particular concentrations of iAs+MMA+DMA) were relatively low compared with foreign data.

Intoxication by large amounts of barium nitrate overcome by early massive K supplementation and oral administration of magnesium sulphate.

Suicide by ingestion of barium is exceptionally rare. Adverse health effects depend on the solubility of the barium compound. Severe hypokalemia, which generally occurs within 2 hours after ingestion, is the predominating feature of acute barium toxicity, subsequently leading to adverse effects on muscular activity and cardiac automaticity. We report one case of acute poisoning with barium nitrate, a soluble barium compound. A 75-year-old woman was hospitalized after suicidal ingestion of a burrow mole fumigant containing 12.375 g of barium nitrate. About 1 hour post-ingestion, she was only complaining of abdominal pain. The ECG recording demonstrated polymorphic ventricular premature complexes (VPCs). Laboratory data revealed profound hypokalemia (2.1 mmol/L). She made a complete and uneventful recovery after early and massive potassium supplementation combined with oral magnesium sulphate to prevent barium nitrate absorption.

Interpretation of hair findings in children after methadone poisoning.

Methadone is not licensed for use in children though it can be employed for the management of neonatal opiate withdrawal syndrome. During the last 2 years, our laboratory has been asked to test for methadone and EDDP, its major metabolite, in hair from children that were admitted to hospital unconscious and where methadone had already been identified in a body fluid (4 cases) or where the children were deceased and evidence of methadone overdosage having already been established (2 cases). In all of these cases, segmental analysis revealed approximately the same amount of drug along the hair lock. As a consequence, contamination was considered as an issue and interpretation of the results was a challenge that deserves particular attention. After decontamination with dichloromethane and segmentation the hair was cut into small pieces, incubated overnight at 40 degrees C, liquid-liquid extracted and analysed with LC-MS/MS, using 2 transitions per compound. The LOQ for both methadone and EDDP was 10 pg/mg. In the first series involving children admitted to hospital, the following results were obtained: * case 1: 4 x 1 cm section, methadone at 0.05-0.08 ng/mg, no EDDP detected, * case 2: 4 x 1 cm section, methadone at 0.13-0.15 ng/mg, EDDP at 0.02 ng/mg, * case 3: 3 x 1.5 cm section, methadone at 0.07-0.09 ng/mg, EDDP at 0.01-0.03 ng/mg, * case 4: 6 x 2 cm section, methadone at 0.06-0.13 ng/mg, EDDP at 0.02-0.03 ng/mg. The following concentrations were obtained from the children who had died following a methadone overdose: * case 5: 2 x 2 cm section, methadone at 0.53-0.58 ng/mg, no EDDP detected, * case 6: 4 x 1 cm section, methadone at 0.44-0.77 ng/mg, EDDP at 0.04-0.06 ng/mg. The first observation is that all these concentrations are low by comparison with those observed in adults on methadone maintenance therapy. However, the more surprising observation is the relative homogenous concentrations along the hair locks in each specific case. This raises concerns around the possibility that contamination could have occurred prior to sampling and makes it hard to reach a conclusion regarding the possibility of repeated methadone exposure in the months prior the incidents. In these cases it was impossible to conclude that the children were deliberately administered methadone. The results of the analysis of hair could indicate that they were in an environment where methadone was being used and where the drug was not being handled and stored with appropriate care. The homogenous concentrations found on segmental analyses could be indicative of external contamination that may have arisen not only from direct contamination with the drug but also via contamination with body fluids at the post mortem or from sweat produced close to the time of the incident. In view of these results we concluded that a single determination should not be used firmly to discriminate long-term exposure to a drug.

Hair analysis to demonstrate administration of sildenafil to a woman in a case of drug-facilitated sexual assault.

The drug sildenafil (Viagra, Pfizer) and, more recently, tadalafil (Cialis, Lilly-Icos) and vardenafil (Levitra, Bayer), has drawn public attention to aphrodisiacs. The search for such substances dates back millennia. Adverse effects associated with these drugs include hypotension, tachycardia, headache, flushing, blurred vision, dyspepsia, and musculoskeletal pain. Although sildenafil has been marketed for erection of the penis, recent attention has been paid to its application for women, including enhancement of success of in vitro fertilization but also better sexual responses (increased desire, satisfaction, and orgasm) in cases of sexual disorders. Today, there is a debate on internet forums about the potential properties of sildenafil to enhance women's sexual pleasure. This laboratory was asked to analyze a 12-cm length of light brown hair submitted by a British police force following an allegation that a young female had been subjected to sexual assaults over a two-year period. The female was 15-17 years of age at the time. The alleged perpetrator was her stepfather, and there was some suspicion that drugs may have been administered to facilitate the attacks. After decontamination and segmentation (6 x 2-cm section), the specimen was analyzed by liquid chromatography coupled with tandem mass spectrometry after alkaline (pH 9.5) extraction using dichloromethane/ isopropanol/n-heptane (25:10:65, v/v/v). The limit of quantitation was 5 pg/mg. The proximal segment tested positive for sildenafil at 38 pg/mg, and all others proved negative. This was in accord with the victim's claim. In the absence of any controlled studies, it was impossible to put any quantitative interpretation on the measured concentration.

Smoking cessation with varenicline: a suicidal fatality.

The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioral and/or cognitive counseling to improve abstinence rates. Varenicline (Champix in France and the U.K.), the most recently approved agent for tobacco cessation, is the first drug in a new class (alpha4beta2 partial agonist) that binds to the nicotinic receptors to release dopamine and alleviate withdrawal symptoms. As the literature reports psychiatric disorders being linked to varenicline as an issue, we describe the case of a man who committed suicide while receiving therapy with this drug. The deceased (a 39-year-old man) was found dead at his home address with slash wounds to his wrist. The deceased had been prescribed varenicline for several months at a dose of 1 tablet (1 mg) twice daily. The lab received a blood specimen to perform a screening for unknown drugs, including varenicline. Because of its selectivity and sensitivity, liquid chromatography coupled to tandem mass spectrometry was chosen as the best approach to develop a procedure for varenicline. One milliliter of blood was extracted with 5 mL of a mixture of dichloromethane/isopropanol/n-heptane (25:10:65) at pH 9.5 (phosphate buffer) in the presence of diazepam-d(5), which was used as an internal standard (IS). The resultant blood extract was separated on an XTerra MS C18 column using a gradient of acetonitrile and formic acid in water. Drugs were identified by three or two transitions (m/z 212 > 169, 212 > 183, and 212 > 195 and 290 > 154 and 290 > 198 for varenicline and IS, respectively). The limit of quantitation of varenicline was 1 ng/mL. The concentration of varenicline in the blood was determined to be 10 ng/mL. This concentration could not be compared with therapeutic levels, as there are no therapeutic concentrations reported in the literature. Because of its potential effects on behavior, the influence of the drug on the mental functioning of the user should be considered in cases of suicide.

Evaluation of the Cozart DDSV test for cannabis in oral fluid.

Saliva or "oral fluid" has been presented as an alternative matrix to establish drug exposure. The noninvasive collection of an oral fluid sample, which is relatively easy to perform and can be achieved under close supervision, is one of the most important benefits when testing for driving under the influence of drugs. Moreover, the detection of Delta9-tetrahydrocannabinol (THC) in oral fluid is a better indication of recent use than a positive urine test, so there is a higher probability that the subject is experiencing pharmacological effects at the time of sampling. Twenty-five subjects (5 free and 20 addicts from a heroin detoxification center) were included in a study to evaluate the potential application of a new device, the Cozart DDSV (drug detection system visual), to detect cannabis in oral fluid. The time cannabis was last smoked was recorded by the medical staff after interview with each subject. Samples were collected with the Cozart DDS Oral Swab and diluted with the Cozart DDS buffer as proposed by the manufacturer. The Cozart DDSV test was conducted on site at the time of collection, and the remainder of the sample retained for confirmation analysis by gas chromatography with mass spectrometry (GC/MS) after methylation of THC (limit of quantitation 0.5 ng/mL). All 25 samples were analyzed by GC/MS. On-site results were obtained within 10 minutes. The 5 drug-free subjects were negative for cannabis, irrespective of the method. From the 20 subjects declaring that they had smoked cannabis between 30 minutes and 24 hours previously, the DDSV device identified 8 positive subjects (with THC concentrations in the buffer in the range 15-219 ng/mL), whereas 18 subjects tested positive using GC/MS. THC concentrations in the Cozart buffer using GC/MS analysis ranged from 0.7 to 219 ng/mL. These concentrations represent about one third the authentic THC concentrations in oral fluid due to the dilution by the liquid of the device. Given the results, the DDSV device was considered as an acceptable tool to detect cannabis abuse in oral fluid within a period of 2-3 hours after smoking.

Chemical abuse in the elderly: evidence from hair analysis.

The use of a drug to modify a person's behavior for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, robbery) has caused some alarm in the general public. Drugs involved can be pharmaceuticals such as benzodiazepines (flunitrazepam, lorazepam, clonazepam), hypnotics (zopiclone, zolpidem), sedatives (neuroleptics, some antihistamines), or anesthetics (GHB, ketamine); drugs of abuse such as cannabis, ecstasy, or LSD; or, more often, ethanol. Mistreatment of older people, whether it is abuse or neglect, can be classified as physical, psychologic, or financial/material. Several types of mistreatment may occur simultaneously. Very few data are available in the international literature. It seems that mental abuse and neglect are more frequent, but physical abuse such as beating, pushing, kicking, and possibly sexual abuse have also been reported. Drugs used to facilitate sexual assaults can be difficult to detect (active products at low dosages, chemical instability), can possess amnesic properties, and can be rapidly cleared from the body (short half-life). In these situations, blood, or even urine, can be inadequate. This is the reason why some laboratories have developed an original approach based on hair testing. Hair was suggested as a valuable specimen in situations in which, as a result of a delay in reporting the crime, natural processes have eliminated the drug from typical biologic specimens. Hair analysis may be a useful adjunct to conventional drug testing in sexual assault. It should not be considered as an alternative to blood and urine analyses, but as a complement. Mass spectrometry/mass spectrometry technologies appear to be required for analyses in drug-facilitated cases. The experience of the authors is presented in cases involving the elderly and chemical poisoning.

Ethyl glucuronide: unusual distribution between head hair and pubic hair.

Ethyl glucuronide (EtG) is a minor metabolite of ethanol that can be detected in hair. In some specific situations, head hair can be missing, and therefore, alternative anatomical locations of hair are of interest. In this study, paired hair specimens (head hair and pubic hair) from eight social drinkers were analyzed for EtG. Each sample was decontaminated by two dichloromethane bathes (5 ml) for 2 min. After cutting into small pieces, about 50 mg of hair was incubated in 2 ml water in the presence of 10 ng of EtG-d5, used as internal standard and submitted to ultra-sonication for 2 h. The aqueous phase was extracted by SPE using Oasis MAX columns. The hair extract was separated on an ACQUITY BEH HILIC column using a gradient of acetonitrile and formate buffer. Detection was based on two daughter ions: transitions m/z 221-85 and 75 and m/z 226-75 for EtG and the IS, respectively. This laboratory is using a positive cut-off at 50 pg/mg. All eight head hair specimens were negative for EtG at a limit of quantitation fixed at 10 pg/mg. Surprisingly, EtG was identified at high concentrations in pubic hair, in the range 12-1370 pg/mg. It appears, therefore, that it is not possible to document the drinking status of a subject by simply switching from head hair to pubic hair.