Current status of hair analysis in forensic toxicology in China

Hair analysis has been mainly used to document drug use history in abusers,drug-facilitated crime cases,doping control analysis and postmortem toxicology in the fields of forensic toxicology,clinical toxicology,and doping control.Hair analysis has also gained more attention in the last 30 years in China.Relevant technology has been promoted as more research has appeared concerning hair analysis,and consensus has been sought among forensic toxicologists regarding aspects such as hair decontamination treatment,detection of abused substances in hair,segmental hair analysis and interpretation of analytical results.However,there are still some limitations in the estimation of drug intake time and frequency by segmental hair analysis due to the different growth cycles evident within a bundle of hairs,the drug incorporation mechanism and sampling errors.Microsampling and imaging mass spectrometry(iMS)technology based on a single hair may be a good choice to estimate drug intake time more accurately.Analysis of hair root samples may also be used to document acute poisoning in postmortem toxicology,and the analysis of the hair shaft can document long-term use of drugs depending on the length of the hair being evaluated.

Portugal's first major forensic case and the genesis of forensic toxicology:10 years of research to reconstruct the event

The"Crime of Flores Street"is one of the most famous cases of poisoning to divide public opinion in Portugal in the late 19th century, and it also demonstrated the weaknesses of the Portuguese medicolegal system and attested to the importance of toxicological analysis. Vicente Urbino de Freitas was a prominent doctor, graduating from the Faculty of Medicine of the University of Coimbra in 1875. He later became Professor of Physiology at the Porto Medical-Surgical School and author of a number of books on leprosy. In 1877, he married Maria das Dores Basto Sampaio Freitas, and this was followed by the death of a number of her close relatives in suspicious circumstances, notably her brother José António Sampaio Junior and nephew Mário Guilherme Augusto de Sampaio. This review aims to retell the story of Portugal's first significant medicolegal case as well as the accompanying judicial drama that gave birth to Forensic Toxicology in Portugal and prompted the medicolegal organization that exists today. This research was carried out over a 10-year period and repre-sents undeniable historical value given the rarity of the facts compiled. At the heart of this forensic case was the use of toxicological analyses in court for which the Chemist Antònio Joaquim Ferreira da Silva played a key role. This toxicological report revealed high concen-trations of morphine, delphinine and narceine in viscera and in Mario's urine. The Mario's cause of death was attributed to poisoning by opium alkaloids. Despite the strong judicial evidence, doubts still remains as to whether Vicente Urbino de Freitas was a"monster"or a victim of circumstances and a hapless martyr.

One image is worth more than a thousand words:producing an atlas of medical signs for teaching clinical and forensic toxicology

Clinical and forensic toxicology are critically involved in the acquisition of basic skills to correctly suspect intoxication,collect biological and non-biological materials for toxicological analysis,comprehend the complexities inherent to laboratory activity,and understand the fundamentals of toxicokinetics and toxicodynamics that underlie the interpretation of results.This works presents a pedagogical innovation proposal for the teaching of clinical and forensic toxicology based on a compilation of more than 3000 cases where the image was fulcra for suspicion.The experience in this article follows the model practiced in bachelors,masters,and PhD degrees,as well as in other continuing training courses,where we are teaching toxicology for more than 15 years.All these levels of education are considered fundamental to the sound development of this science.This approach aims also to offer strength to the intervention of the true toxicologist in all the toxicological phases,besides the classic analytical chemistry.Indeed,it is impossible to provide effective clinical and forensic toxicological interpretations without a proper and broad education,and not thinking exclusively in terms of laboratory techniques.In the future,it will be interesting to evaluate knowledge retention and to propose a database of videos of signs related to intoxications.

Hyphenated Techniques in Liquid Chromatography and their Applications in Forensic Toxicology:A Review

Conventional analytical methods,such as gas chromatography,high performance liquid chromatography(LC),ultra-violet,and others,are ineffective in addressing the increasing number of problems in forensic toxicology.Hyphenated analytical methods,wherein the separation method are coupled or combined with spectral methods,with the help of a proper interface,are the available alternative options.The key benefits of these methods are the requisites of low limits for detection,shorter analytical time,the possibility of automation,better reproducibility,and high precision and repeatability.This review discusses on some of the hyphenated analytical methods that involve LC as the separation tool,for their most recent applications in the area of forensic toxicology focusing on the screening of drugs of abuse,the usage of alternative matrices for monitoring drug abuse,analysis of chemical warfare agents,determination of doping agents and related substances,natural toxins,environmental poisons,and examination of food produce adulteration.The incorporation of the more user-friendly LC-interfaces,such as atmospheric pressure chemical ionization,and electrospray ionization in the LC-mass spectrometry has increased the popularity of this technique tremendously among scientists of different disciplines.Hyphenated approaches have extremely low constraints regarding the identification and quantification,and offer high reproducibility,with unparalleled potential.

Analysis of Nine Cases of Acute Thallium Poisoning

In this study nine cases of thallium poisoning in a series of homicidal poisoning were analyzed in order to provide more information concerning thallium poisoning. It was found that the most common clinical feature of thallium poisoning was peripheral neuropathy and paraesthesia was more common than amyasthenia. Understanding of these clinical characteristics of thallium poisoning was helpful to early identification and differential diagnosis. Since the early administration of Prussian Blue, as a specific antidote for thallium poisoning, can substantially improve the prognosis, it is of great importance to establish a correct and early diagnosis.

Effects of Aconitine on [Ca^(2+)] Oscillation in Cultured Myocytes of Neonatal Rats

In order to investigate the effects of aconitine on [Ca2＋] oscillation patterns in cultured myocytes of neonatal rats, fluorescent Ca2＋ indicator Fluo-4 NW and laser scanning confocal micro- scope （LSCM） were used to detect the real-time changes of [Ca2＋] oscillation patterns in the cultured myocytes before and after aconitine （1.0 μmol/L） incubation or antiarrhythmic peptide （AAP） and aconitine co-incubation. The results showed under control conditions, [Ca2＋] oscillations were irregu- lar but relatively stable, occasionally accompanied by small calcium sparks. After incubation of the cultures with aconitine, high frequency [Ca2＋] oscillations emerged in both nuclear and cytoplasmic regions, whereas typical calcium sparks disappeared and the average [Ca2＋] in the cytoplasm of the cardiomyocyte did not change significantly. In AAP-treated cultures, intracellular [Ca2＋] oscillation also changed, with periodic frequency, increased amplitudes and prolonged duration of calcium sparks. These patterns were not altered significantly by subsequent aconitine incubation. The basal value of [Ca2＋] in nuclear region was higher than that in the cytoplasmic region. In the presence or absence of drugs, the [Ca2＋] oscillated synchronously in both the nuclear and cytoplasmic regions of the same cardiomyocyte. It was concluded that although oscillating strenuously at high frequency, the average [Ca2＋] in the cytoplasm of cardiomyocyte did not change significantly after aconitine incuba- tion, compared to the controls. The observations indicate that aconitine induces the changes in [Ca2＋] oscillation frequency other than the Ca2＋ overload.

Guidelines for Collection of Biological Samples for Clinical and Forensic Toxicological Analysis

This article aims to review general procedures for sampling of routinely collected as well as on alternative samples that may provide additional information regarding intoxication.These approaches may be applied whenever sample collection for clinical and forensic toxicology is required and should be considered as general guidelines that must be adapted to each specific case.It is expected that this article will help toxicologists and other forensic experts to accomplish their mission,since the toxicological result is first influenced by the quality and quantity of the sample available for analysis.These guidelines were approved by the European Council of Legal Medicine.

Analysis of the testimonial evidence of Portugal's first major forensic case:part Ⅱ

The crime possibly perpetrated by a doctor named Vicente Urbino de Freitas in 1890 is one of the most famous cases of poisoning,and it had echoes in the Portuguese and foreign press for several decades.This prestigious doctor was convicted of the fatal poisoning of his nephew.He also attempted the homicide of two nieces and their mother-in-law,who only escaped because they obstinately refused to comply with the"therapeutics"prescribed by the family doctor.The motive of the crime should have been Vicente Urbino de Freitas'ambition to receive the family inheritance of his wife,the daughter of the well-known mer-chant Jose Antonio Sampaio of Flores Street in Porto.Vicente Urbino de Freitas was con-victed but doubt about his guilt persists for more than a century.This second work aimed to collect and analyse all the relevant and contradictory testimonial evidence of the prosecu-tion and defence witnesses.This case represents an odd historical record obtained through more than 12years of research on the first major significant Portuguese forensic case.Rare and unprecedented testimonial evidence and photographs were obtained from different countries and then repaired,since these also provide an important historical record of the medical photography.

Gabapentin prevalence:clinical and forensic experience in St.Louis,Missouri,USA

Gabapentin(Neurontin)is an anti-epileptic drug that has had wide off-label prescription use since market release due to presumed negligible abuse potential.However,trends in drug misuse have demonstrated that gabapentin misuse is occurring,particularly in those with a history of opioid misuse.This is concerning,because although gabapentin has no direct ligand activity at opioid receptors,it does potentiate the analgesic effect of opioids,and concurrent use of gabapentin and opioids may increase the risk of respiratory depressive effects of opioids.This study investigates the incidence of gabapentin detected in urine samples collected for clinical drug screening purposes in a local hospital emergency department and in postmortem samples submitted by medical examiners in the St.Louis metropolitan area.The prevalence of gabapentin and co-detected drugs in both populations is contrasted,compared,and discussed.This study found that 30%of urine samples collected from patients with suspected drug intoxication presenting to SSM Health Saint Louis University Hospital,a quaternary care medical center,were positive for gabapentin,and nearly two thirds of those were also positive for oxycodone.Over a 6-month period,the incidence of gabapentin positive postmortem cases increased from 18%to 20%.Nearly all gabapentin positive postmortem cases were also positive for an opioid,the most significant being fentanyl,suggesting that gabapentin misuse may be due to its potentiating effect of opioid drug action.This study also highlights the limited utility of immunoassay-based urine drug screens.

Epidemio-toxicological profile of suicide cases:analysis from a forensic unit in Brazil

The suicide phenomenon involves complex interactions between psychological,biological,cultural and socio-environmental factors.This study aimed to assess the epidemiological and toxicological profiles of officially confirmed suicide victims.Aretrospective study was performed using autopsy reports,forensic anthropology examinations and police summaries of all suicide cases that underwent toxicological analysis at an Official Forensic Laboratory(Minas Gerais,Brazil)in 1 year.The sample set was composed of 351 suicide victims,predominantly men(70.32%),most of them were adults between 31 and 64 years old(62.11%),with mixed skin colour(48.89%)and low educational level(66.44%).The most common suicide method was hanging(57.79%),followed by intoxication(30.45%).Most victims presented positive toxicological results(56.41%),especially for the presence of medicines(37.6%),illicit drugs(36.3%)and pesticides(26.1%).Our study corroborated previous data that most suicide victims have low educational levels.The most common toxicological findings were medicines,especially prescription drugs,followed by illicit drugs and pesticides.We hope this study contributes to reflections and planning of preventive suicide programmes,considering the described profiles of victims.

Forensic toxicological study on adipocere formation in submerged cadavers of female albino rats intoxicated with cadmium

There is a dearth of information on the mutual interaction between metal intoxication and adipocere formation.Herein,40 adult female albino rats were distributed into two equal groups,one used as control while the other orally administered single dose of cadmium chloride(CdCl_(2))225mg/kg·bw(LD_(min)).Control group was killed by cervical dislocation.Half of dead rats of both groups were subjected for determination of iodine value and estimation of cadmium(Cd)residues while the other half of both groups were submerged in opened glass container previously filled with 4L dechlorinated tap water kept in closed room with an open air access(one cadaver/container).Gross morphological changes of submerged cadavers were recorded weekly along the experiment.At the end of the experiment,after 3months,samples were collected again for iodine value determination and estimation of Cd residues.The obtained results revealed the depressant effect of Cd toxicity on development of adipocere.Cd residues were found in different tissues of cadavers at time of death with the highest amount in the intestines followed by the liver and kidneys,then lungs,adipose tissue,muscles,and finally the bones.After 3months of water submersion,tissues exhibited significant decrease in the amount of Cd residues but to a limit that was still detected.This study concluded the possibility of detection of Cd residues even after adipocere formation.Additionally,it shed light on the possibility of the interference of environmental pollution with the natural rate of decomposition especially adipocere formation.

Fatal Carbon Monoxide Poisoning

Liquefied petroleum gas on combustion with deficient oxygen produces toxic carbon monoxide.It is used as a fuel to heat water in gas geysers.Here,we report a fatal case of carbon monoxide poisoning resulting from the usage of gas water heater.A 24-year-old female had gone to take bath in a bathroom where a gas geyser was installed to heat the water.As she did not come out of the bathroom even after more than an hour,the door was broken down by the relatives and she was found dead.Cherry red postmortem hypostasis,congested and edematous pinkish lungs,and cerebral edema were salient autopsy findings.Carboxyhemoglobin was quantified in blood to 76.55%.The cause of death was attributed to carbon monoxide poisoning;accidental in manner.This case highlights the hazards of using a gas geyser in an ill-ventilated bathroom.

Wastewater analysis for nicotine,cocaine,amphetamines,opioids and cannabis in New York City

According to current surveys and overdoses data,there is a drug crisis in the USA.Wastewater-based epidemiology(WBE)is an evolving discipline that analyses wastewater samples to detect drugs and metabolites to estimate drug consumption in a certain community.This study demonstrates how drug relative presence could be tracked by testing wastewater,providing real-time results,in different boroughs in New York City throughout 1 year.We developed and fully validated two analytical methods,one for 21 drugs and metabolites,including nicotine,cocaine,amphetamines,opioids and cannabis markers;and another for the normalization factor creatinine.Both methods were performed by liquid chromatography tandem mass spectrometry(LC-MS/MS)using positive electrospray ionization,achieving a limit of quantification of 5–10 ng/L for drugs and metabolites,and 0.01 mg/L for creatinine.These methods were applied to 48 one-time grab wastewater samples collected from six wastewater treatment plants in New York City(Manhattan,The Bronx,Queens and Brooklyn),eight different times throughout 2016,before and after major holidays,including Memorial Day,4th of July,Labour Day and New Year’s.In this study,the drug group normalized concentrations present in the wastewater samples,in decreasing order,were cocaine,nicotine,opioids,cannabis and amphetamines.When looking at individual compounds,the one with the highest normalized concentration was benzoylecgonine(BE),followed by cotinine,morphine and 11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH).To estimate community use,these concentrations were multiplied by the corresponding correction factor,and the most present were THCCOOH,followed by BE,cotinine and morphine.When comparing the treatment plants by drug group(nicotine,cocaine,amphetamines,opioids and cannabis),samples collected from The Bronx had the highest normalized concentrations for nicotine,cocaine and opioids;The Bronx and Manhattan for cannabis;and Manhattan and Queens for amphetamines.In most of the cases,no effect due to holiday was observed.This study provides the first snapshot of drug use in New York City and how that changes between key calendar dates employing wastewater analysis.

Determination of amphetamines,ketamine and their metabolites in hair with high-speed grinding and solid-phase microextraction followed by LC-MS

A novel hair sample pre-treatment method based on high-speed grinding and solid-phase microextraction(SPME)had been applied for the determination of amphetamines,ketamine and their metabolites in hair samples by liquid chromatography mass spectrometry(LC-MS).A 20mg sample of hair was ground with 2 mL of saturated sodium carbonate solution using a high-efficiency hair grinder with 70 Hz osillation for 2min at 4℃.After centrifuging,1.5mL of the supernatant was transferred and treated with SPME by direct immersion(DI-SPME).The target analytes extracted by fibre were desorbed and analysed using LC-MS.Under the optimum conditions,a recovery of 90.2%-95.8%was obtained for all analytes.The analytical method was linear for all analytes in the range from 0.2 to 10 ng/mg with the correlation coefficient ranging from 0.9985 to 0.9993.The detection limits for all analytes were estimated to be 0.067 ng/mg.The accuracy(mean relative error)was within±6.9%and the precision(relative standard error)was less than 6.8%.The combination of high-speed grinding of hair and SPME had the advantages of being easy to perform,environment-friendly and high in detection sensitivity.The proposed method offered an altermative ana lytical approach for the sensitive detection of drugs in hair samples for forensic purposes.

Fatalities caused by novel opioids:a review

Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the action of this naturally occurring analgesic.Most of these are based on fentanyl structures that are much more potent,and dangerous,than fentanyl itself.This publication reviews reports of fatalities attributed to 15 novel opioids with the view to assessing mortality associated with their misuse as well as reviewing published analytical procedures that would be able to detect these and other novel opioids.These drugs include reports of deaths to acetylfentanyl,acrylfentanyl,butr(yl)fentanyl,carfentanil,2-and 4-fluorofentanyls,4-fluorobutyrfentanyl,4-fluoroisobutyrfentanyl,furanylfentanyl,a-and 3-methylfentanyls,4-methoxyfentanyl,ocfentanil,as well as AH-7921,U-47700 and MT-45.Most of these cases reporting a drug-caused death involved other drugs in addition to the opioid.No obvious minimum fatal concentration was discerned for any of the opioids for which details were provided,however,the more potent members required detection limits well under 1 ng/mL and often even well below 0.1 ng/mL requiring use of the most sensitive mass spectral detection procedures,particularly when screening specimens using a non-targeted mode.Four other novel opioids have been reported in admissions to hospitals include 4-chloroisobutryfentanyl,cyclopentylfentanyl and tetrahydrofuranfentanyl,all of which are likely to have the potential to cause death.It is also likely that other analogues will appear with time.

Simultaneous determination of free methamphetamine,pethidine,ketamine and tramadol in urine by dispersive liquid–liquid microextraction combined with GC–MS

A simple and rapid dispersive liquid–liquid microextraction(DLLME)technique coupled with gas chromatography–ion trap mass spectrometry(GC–MS)was developed for the extraction and analysis of methamphetamine(MA),pethidine(PD),ketamine(KT)and tramadol(TD)from human urine.In this study,different parameters affecting the extraction process such as the type and volume of extraction solvent,type and volume of disperser solvent,extraction time and pH value and salt effect were studied and optimized.Under optimized conditions,the enrichment factor ranged from 185 to 226 and the average recovery ranged from 80.45%to 95.55%.The linear range was 10.0–1000.0 mg/L,the limit of detection and quantitation were in the range 0.43–1.96 mg/L and 1.44–6.53 mg/L,respectively.The relative standard deviations were in the range 1.98%–3.90%(n=7).The obtained results show that DLLME combined with GC–MS is a fast and simple method for the determination of MA,PD,KT and TD in human urine.

Quantitative analysis of opioids and cannabinoids in wastewater samples

Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in defined population groups.We developed and validated an analytical method for the simultaneous determination of opioids(morphine,oxycodone,hydrocodone,oxymorphone and hydromorphone),and cannabinoids(△9-tetrahydrocannabinol,11-nor-9-carboxy-tetrahydrocannabinol(THCCOOH)and THCCOOH-glucuronide)in raw-influent wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry.Method validation included linearity(5-1000 ng/L for opioids,10-1000 ng/L for cannabinoids),imprecision(<21.2%),accuracy(83%-131%),matrix effect(from-35.1%to-14.7%)and extraction efficiency(25%-84%),limit of detection(1-5 ng/L)and quantification(5-10 ng/L)and auto-sampler stability(no loss detected).River and wastewater samples were collected in triplicate from different locations in New York City and stored at-20℃until analysis.Water from sewage overflow location tested positive for morphine(10.7 ng/L),oxycodone(4.2-23.5 ng/L),oxymorphone(4.8 ng/L)and hydromorphone(4.2 ng/L).Raw influent wastewater samples tested positive for morphine(133.0-258.3 ng/L),oxycodone(31.1-63.6 ng/L),oxymorphone(16.0-56.8 ng/L),hydromorphone(6.8-18.0 ng/L),hydrocodone(4.0-12.8 ng/L)and THCCOOH(168.2-772.0 ng/L).This method is sensitive and specific for opioids and marijuana determination in wastewater samples.

Metabolism and metabolomics of ketamine:a toxicological approach

Ketamine is a phencyclidine derivative and a non-competitive antagonist of N-methyl-D-aspartate(NMDA)receptor for which glutamate is the full agonist.It produces a functional dissociation between the thalamocortical and limbic systems,a state that has been termed as dissociative anaesthesia.Considerable variability in the pharmacokinetics and pharmacodynamics between individuals that can affect dose-response and toxicological profile has been reported.This review aims to discuss pharmacokinetics of ketamine,namely focusing on all major and minor,active and inactive metabolites.Both ketamine optical isomers undergo hepatic biotransformation through the cytochrome P450,specially involving the isoenzymes 3A4 and 2B6.It is first N-demethylated to active metabolite norketamine.Different minor pathways have been described,namely hydroxylation of the cyclohexanone ring of ketamine and norketamine,and further conjugation with glucuronic acid to increase renal excretion.More recently,metabolomics data evidenced the alteration of several biological pathways after ketamine administration such as glycolysis,tricarboxylic acid cycle,amino acids metabolism and mitochondrial b-oxidation of fatty acids.It is expected that knowing the metabolism and metabolomics of ketamine may provide further insights aiming to better characterize ketamine from a clinical and forensic perspective.

Determination of 3-MeO-PCP in human blood and urine in a fatal intoxication case,with a specific focus on metabolites identification

3-Methoxyphencyclidine(3-MeO-PCP)is a new psychoactive substance that belongs to the phencyclidines family,first identified in Europe in 2012.This drug presents a stronger binding to N-methyl-D-aspartate(NMDA)receptors when compared to phencyclidine,which results in more potent effects,even at low concentrations.Very few articles have been published regarding 3-MeO-PCP in forensic toxicology.In this paper,the authors present a fatal 3-MeO-PCP intoxication case.In addition to the detection of the parent drug,metabolites were investigated in urine and,for the first time in the scientific literature,in blood.3-MeO-PCP and its metabolites were quantitated by liquid chromatography-tandem mass spectrometry system(LC-MS/MS).Identification was confirmed by liquid chromatography-high resolution mass spectrometry(LC-HRMS).3-MeO-PCP tested positive in femoral blood(3525 ng/mL)and urine(7384 ng/mL).The femoral blood concentration was higher than the fatal concentrations range already reported in the literature(from 50 to 3200 ng/mL).3-MeO-PCP metabolites,including O-demethyl-3-MeO-PCP,piperidine-OH-3-MeO-PCP,O-demethyl-piperidine-di-OH-3-MeO-PCP and piperidine-di-OH-3-MeO-PCP,were detected in blood.In addition,two new metabolites,O-demethyl-piperidine-OH-3-MeO-PCP and O-demethyl-cyclohexyl-OH,were identified in both blood and urine.Unfortunately,due to the lack of reference material on the market,it was not possible to measure the concentration of these metabolites.However,the ratios between the metabolites and the parent drug were useful to estimate their analytical response and prevalence.At this time,considering the low ratios(<1)between metabolites and parent drug,metabolites testing does not seem useful to increase the detection window of the drug.

Identification of adrafinil and its main metabolite modafinil in human hair.Self-administration study and interpretation of an authentic case

For several years,the misuse of stimulant substances is increasingly observed both in the field of sport,to improve the functions of the body and therefore to be more performant,and also by non-athletes to make life more tolerable on a daily basis.Adrafinil,2-((diphenylmethyl)sulfinyl)-N-hydroxyacetamide,is a drug designed for the treatment of narcolepsy by promoting an awakened state,and to treat alertness and neurological symptoms in the elderly.It is primarily metabolized in vivo to an active form,i.e.modafinil,2-((diphenylmethyl)sulfinyl)acetamide.The World Anti-Doping Agency(WADA)banned these two drugs in sports in 2004.The authors report an authentic case involving adrafinil and modafinil.The laboratory was requested to test for adrafinil in a hair strand collected from a woman found in posses-sion of vials of adrafinil and suspected of trafficking.A specific method was developed by liquid chromatography tandem mass spectrometry(LC-MS/MS).Unlike modafinil(varying from 6.8 to 13.9ng/mg),adrafinil was not identified in the strand.The interpretation of the results was difficult because this is the first case describing human hair analysis.In order to be able to interpret the results,a self-administration study was conducted after an oral administration to a volunteer(200 mg)whose beard hair was collected 10days after adminis-tration.The analysis of this specimen highlighted the presence of adrafinil at 0.8ng/mg and modafinil at 0.5 ng/mg.These results demonstrate the dual identification of both compounds after a single consumption,even after administration of a low dose.According to these results,the analysis of the hair strand from the authentic case does not match with a con-sumption of adrafinil,in accordance with abuse of modafinil alone.Intelligence considered that this was a trafficking case of adrafinil,with no self-consumption.