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.
•- Chemical submission can affect victims of all ages not only youngest.•- Toxicological analyzes using appropriate methods are mandatory for diagnosis.•- The name “date-rape drug” is wrongly ...attributed to GHB (less than 4% of our cohort)•- Benzodiazepines deserve this naming due to their highest prevalence each year.
Drug facilitated-crime or chemical submission (DFC/CS) is defined as the concealed or forced administration of psychoactive substances to a victim for criminal purposes. This is a national program set up in the early 2000s in the form of a prospective multicenter survey, the results of which this manuscript presents. Over this 19-year period, 5487 cases were collected, analyzed and classified into 54% of suspected cases, 29% of chemical vulnerability (CV) cases and 17% of proven DFC/CS cases. In the overall data, the most prevalent victims were female (81%), with an average age of 27 years. Sexual assault was the most frequent aggression (77%), followed by theft (14%).
Victims of proven DFC/CS cases were from of all ages including children and elderly. In 934 victims of DFC/CS, 100 various psychoactive substances were detected mostly represented by benzodiazepines and z-drugs (55%), various sedatives including antihistamines (16%) and non-therapeutic substances (16%). Gamma-hydroxybutyric acid (GHB) was found in 4% cases. In CV cases, alcohol (90%) and cannabis (32%) intake were mainly involved
In France, despite prevention messages, DFC/CS has been an epidemic for many years and has been proven by our national study. This national program has the aim to identifying the substances used but unfortunately not the goal to fight against this phenomenon. Since 2009, we observed a new modus operandi of the aggressors who pose as taxi drivers facilitating the reception of the victims leaving nightclubs. We can emphasize that GHB is not the “date rape drug” but rather the benzodiazepine class is.
The number of reports on drug facilitated crimes is increasing these last years. Apart from ethanol and cannabis, benzodiazepines (BZD) and analogs are the most common drugs reported to be used ...probably due to their amnesic and sedative properties. We have developed a rapid and sensitive method using LC–MS/MS triple stage quadrupole (TSQ) for the determination of single exposure to bromazepam (Lexomil
®, 6
mg) and clonazepam (Rivotril
®, 2
mg) in urine and hair of healthy volunteers. Chromatography was carried out on a Uptisphere ODB 5
μm, 2.1
mm × 150
mm column (Interchim) with a gradient of acetonitrile and formate 2
mM buffer, pH 3. Urine was extracted with Toxitube A
® (Varian) and allowed the detection of bromazepam, 3-hydroxy-bromazepam, clonazepam and 7-Aminoclonazepam for more than 6 days. Head hair, collected 1 month after the exposure, was treated by incubation with Soerensen buffer pH 7.6, followed by liquid–liquid extraction with dichloromethane for common BZD. A specific pre-treatment for amino-BZD, with an incubation of 15
min at 95
°C in 0.1
N NaOH before liquid–liquid extraction with dichloromethane, gave better recoveries and repeatability. After single exposure, bromazepam was present in powdered hair at 28
pg/mg and 7-Aminoclonazepam at 22
pg/mg in the first 1-cm segment, while no clonazepam was detectable. This method was applied in two forensic cases. It allowed us to determine bromazepam in urine 3 days after the alleged offense and in cut head hair at a concentration of 6.7
pg/mg only in the 2-cm proximal segment. The other case showed the presence of clonazepam and 7-Aminoclonazepam in urine a few hours after the offense and the presence of 7-Aminoclonazepam at about 3.2
pg/mg in axillary hair 4 months later.
The authors present an overview of the drug-facilitated crime (DFC) phenomenon, especially in France. Recently, there has been an increase in reports of incidents (mainly sexual assaults and robbery) ...as well as in scientific publications and congress presentations on the topic. From enquiries conducted nationally, a list of drugs reportedly associated with DFC was established and includes benzodiazepines and benzodiazepine-like drugs (zolpidem, zopiclone), minor tranquilizers and neuroleptics, barbiturates, narcotics, hallucinogens, and anaesthetics. Some of these molecules are specific to France in DFC cases. A study using healthy volunteers who had taken benzodiazepines (lorazepam, bromazepam, flunitrazepam, clonazepam), zolpidem and zopiclone, showed that the only way to increase the duration of detection of these drugs is to use liquid chromatography-tandem mass spectrometry (LC-MS/MS) to test blood and urine samples. The very high sensitivity of this method appears to be an essential condition to document the cases, because the drugs tested were still detectable in urine at least 6 days after the ingestion of one therapeutic dose. Limits of detection were always lower than 0.5 ng/mL in urine. The actual list of molecules and metabolites the authors screened for in urine and blood by LC-MS/MS, in every DFC, is given in detail: 25 benzodiazepines and benzodiazepine-like drugs, 11 minor tranquilizers and neuroleptics, 2 barbiturates, 12 narcotics, 4 hallucinogens, and 1 anaesthetic. However, the distinction between continual therapeutic use of a psychotropic drug or illegal narcotic and a single ingestion has to be documented by sequential analysis of hair, again with LC-MS/MS.
A tendency for re-offending in drug-facilitated crime Chèze, Marjorie; Muckensturm, Aurélie; Hoizey, Guillaume ...
Forensic science international,
03/2010, Volume:
196, Issue:
1
Journal Article, Conference Proceeding
Peer reviewed
Abstract The authors present 3 cases that demonstrate a return to DFC following periods of inactivity. The offences occurred in Paris and its suburbs and in each of the cases there were two distinct ...periods of activity by the offenders with 2, 8 and 22 victims attributed to each of the perpetrators. To 20 mg of decontaminated and cut hair, 100 pg/mg of clonazepam-d4 was added as internal standard. Hair specimens were extracted with CH2 Cl2 /ether after incubation overnight at 56 °C in pH 7.6 buffer. Extractions were performed on blood and urine using Toxi-tube A® with 5 ng/mL of clonazepam-d4. The residues were analyzed by LC–ESI-MS/MS. Calibration curves in blood and urine (0.5–500 ng/mL) were prepared by spiking aliquots of blank fluids ( r2 > 0.9816 for all drugs). LOD in body fluids ranged 0.5–10 ng/mL. Calibration curves in hair (0.5–100 pg/mg) were prepared by spiking aliquots of blank hair ( r2 > 0.9877 for all drugs). LOD in hair ranged 0.5–5 pg/mg. Case #1 : Two young women were raped with an interval of approximately 1 year between the incidents. Lorazepam (present, <2 pg/mg) was detected in hair obtained from the first victim, and zolpidem (19 pg/mg) in hair of the second one. The offender was in jail between the two offences. Case #2 : The offender approached a total of 8 men and women who were aged over 50 years. The offender was in jail between the two series of respectively 3 and 5 victims. Zopiclone was detected in victims’ hair ( n = 7) at concentrations 13–42 pg/mg. Case #3 : The offender stole thousands of Euros using credit cards obtained from 22 different wealthy victims. He employed a cocktail of up to 6 drugs made up of: flunitrazepam, clonazepam, doxylamine, cyamemazine, zolpidem and lorazepam. Drugs were detected in all victims’ hair ( n = 18) at concentrations in the range 1–81 pg/mg for all drugs. Between the two series (of respectively 4 and 16 victims) the offender spent 6 months in jail, and then police spent 6 months looking for him while he was under judiciary control prior to his judgment. Segmental hair analysis permits retrospective information on drug exposure and should be considered in the investigation of drug-facilitated crimes not only to prove single exposure but also when there has been any appreciable delay in samples being obtained for analysis. Indeed, in 56% cases reported in this paper, due to the long time that elapsed between offences and the opportunity to obtain samples for analysis hair analysis was considered the only viable matrix to investigate the possibility of drug involvement in the crimes. Our experience demonstrates that the incidence of re-offending in DFC after a period of inactivity (often due to imprisonment) may be of concern, notably in big cities.
Attempted murder by repeated poisoning is quite rare. The authors describe the case of a 62-year-old man who was admitted to an intensive care unit (ICU) for neurological disturbances complicated by ...inhalation pneumopathy. He presented a loss of consciousness while his wife was visiting him at the ICU (H0). Forty-eight hours later (H48), police officers apprehended the patient's wife pouring a liquid into his fruit salad at the hospital. Toxicological analyses of a blood sample and the infusion equipment (H0), as well as the fruit salad and its container (H48), confirmed the attempted poisoning with cyamemazine (H0) and hydrochloric acid (H48). In order to evaluate the anteriority of poisonings, hair analysis was requested and the medical records of the 6 previous months were also examined. Two 6-cm brown hair strands were sampled and the victim's medical record was seized in order to determine the treatments he had been given during the previous six months. Segmental hair testing on two 6-cm brown hair was conducted by GC-MS, LC-DAD and LC-MS/MS (0–2/2–4/4–6 cm; pg/mg). Haloperidol (9200/1391/227), amitriptyline (7450/1850/3260), venlafaxine (332/560/260), that had never been part of the victim's treatment were detected, as well as some benzodiazepines (alprazolam, bromazepam, nordazepam); cyamemazine was also detected in all the segments (9960/1610/2367) though only a single dose administration was reported in the medical records. The toxicological analyses performed at H0 and H48 confirmed the homicide attempts in the ICU. In addition, comparison of the results in hair analysis with the medical records confirmed repeated poisoning attempts over the previous six months, and thus explain the origin of the disorders presented by the victim. This case serves to remind us that repeated attempted murder can be difficult to diagnose and that hair analysis can be an effective way to detect such attempts.
•Repeated poisoning attempts are currently rare.•Hair analysis compared with medical records documented repeated homicide attempts.•Hair analysis contributed to explain the disorders presented by the victim.•Hair analysis led to rescue of the victim from his aggressor.
Tabernanthe iboga belongs to the Apocynaceae family. In this study, we report the case of a 37-year-old black male working as a security agent in Paris and found dead naked on the beach in Gabon ...after consumption of iboga. Autopsy revealed a drowning fatality and a myocardial abnormality (myocardial bridging). Samples of blood, urine, bile, gastric content, liver, lungs, vitreous, spleen and hair were taken. Biological fluids were liquid-liquid extracted with saturated NH4Cl pH 9.5 and methylene chloride/isopropanol (95/5, v/v) in presence of clonazepam-d(4), used as internal standard. After decontamination with dichloromethane, hair was cut into small pieces then sonicated for 2h in saturated NH4Cl pH 9.5 before extraction by methylene chloride/isopropanol (95/5, v/v). After evaporation the residues were reconstituted in methanol/ACN/formate buffer pH 3, from which 10 microL were injected into an ODB Uptisphere C(18) column (150 mm x 2.1mm, 5 microm) and eluted with a gradient of acetonitrile and formate buffer delivered at a flow rate of 200 microL/min. A Quantum Ultra triple-quadrupole mass spectrometer was used for analyses. Ionization was achieved using electrospray in the positive ionization mode (ESI). For each compound, detection was related to three daughter ions (ibogaine: m/z 311.4-->122.1, 174.1 and 188.1; noribogaine: m/z 297.4-->122.1, 159.1 and 160.1; clonazepam-d(4): m/z 319.9-->218.1, 245.1 and 274.1). Ibogaine and noribogaine were detected in all autopsy samples. Hair segmentation was not possible as hair was very short and frizzy. Concentrations of 1.2 and 2.5 ng/mg, respectively were detected. Neither other licit or illicit drugs nor alcohol were found. The presence of ibogaine and noribogaine in all autopsy samples was consistent with the recent absorption of Tabernanthe iboga, which was assumed to be responsible of the drowning fatality. The history of exposure, regarding hair analysis, is discussed. LC-MS/MS appears to be the best method for analyzing complex and poorly volatile alkaloids in autopsy samples and particularly in hair, due to the presence of a nitrogen ring and the relatively low concentrations to be measured.
Abstract Morphine sulfate misuse is essentially observed among regular heroin injectors. To our knowledge, primary addiction to morphine sulfate is exceptional, especially among young adolescents. A ...13-year-old girl, with no history of addiction, was found dead with three empty blisters of Skenan® LP 30 mg at her side. Opiates were detected in biological fluids and hair by chromatographic methods. Blood analyses confirmed morphine overdose (free morphine: 428 ng/mL; total morphine: 584 ng/mL) and segmental hair analysis confirmed regular exposure over several months (maximum morphine concentration 250 pg/mg). Suspecting the victim's mother of recreational use of Skenan® , the magistrate ordered analysis of her hair, with negative results. From an epidemiological viewpoint, this case of oral morphine sulfate abuse in an adolescent with no previous history suggests the emergence of a new trend of morphine sulfate consumption. From a toxicological viewpoint, it demonstrates the value of hair testing, which documented the victim's regular exposure and made an important contribution to the police investigation.
We have developed a GC-MS-MS assay for GHB in human hair. Five milligrams of washed hair were hydrolyzed by 1M or 0.01M NaOH before a liquid-liquid extraction with ethyl acetate under acidic ...conditions. GHB-d6 was used as the internal standard. TMS derivatives were formed before injection. TBDMS derivatives were used in cases of strong chromatographic interferences or in a confirmatory procedure. Analysis of basal levels of GHB in 61 drug-free donors gave the following results: the mean measured concentration for blond hair was 0.60 ng/mg (n = 12), SD = 0.19 ng/mg, and extreme figures were in the range 0.35–0.95 ng/mg. For brown hair, the mean measured concentration was 0.90 ng/mg (n = 30), SD = 0.42 ng/mg, and extreme figures 0.41–1.86 ng/mg. For black hair, the mean measured concentration was 0.90 ng/mg (n = 19), SD = 0.37 ng/mg, and extreme figures 0.32–1.54 ng/mg, showing no significant differences depending on hair color. Analysis of basal levels of GHB of 12 or more specimens in segmented hair showed a mean concentration of 1.22 ng/mg (0.31–8.4 ng/mg) and a relative standard deviation for each individual ranging from 6.75% to 37.98%. GHB was administered to a healthy 53-year-old white male (light brown hair) at oral dosages of 30, 45, and 60 mg/kg. Beard hair was collected just before administration and 24 h after (and each day for one week for the last dose), and a 7.5-cm scalp hair lock was collected 7 days after the last dose. A rise in GHB concentration was observed in beard hair for the 45 and 60 mg/kg dosages with a maximum at 24 h, whereas no change was observed for the 30 mg/kg dosage. Scalp hair was segmented into 3-mm long segments. The three proximal last segments showed significantly (0.0005 < p < 0.005) different concentrations of GHB (1.22, 1.27, and 1.66 ng/mg, respectively) when compared with the basal physiological level of GHB in this same person (mean = 0.62 ng/mg, SD = 0.15 ng/mg). A case of daily GHB abuse during bodybuilding allowed us to determine a concentration of GHB of 14 ng/mg, in a 2-cm long segment (black hair). A case of rape under the influence of GHB was documented through hair analysis (black hair) and positive analysis of the glass she used. Sampled 7 days after the sexual assault, the three last 3-mm long proximal segments tested for GHB exhibited concentrations of 3.1–5.3 and 4.3 ng/mg, respectively, whereas the mean physiological level determined in this woman was 0.71 ng/mg, SD = 0.17 ng/mg. The authors advise a two-step hair sampling as evidence of GHB consumption: the first sample at the time of exposure to show the contamination by sweat of the proximal segment in case of recent administration with a significant rise of hair level at the root, and the second after at least 3 or 4 weeks to avoid this contamination and determine the levels incorporated in the hair matrix before, during, and after the exposure.
In recent years, reports of drug-facilitated crimes (DFC) have been increasing. The drugs involved are sometimes difficult to detect, because of their low dosages and the long time ellapsed between ...alleged DFC and blood and urine sampling. In order to detect benzodiazepines and benzodiazepine-like hypnotics, we developed an approach for hair analysis by liquid chromatography–tandem mass spectrometry using a triple stage quadrupole with an electrospray ionization (LC–ESI-MS/MS). Separation was performed on an Uptisphere ODB C18 column using a gradient of 2
mM formate buffer and acetonitrile. For the 23 compounds studied, detection limits are lower than 2
pg/mg, but a specific extraction procedure is needed for 7-amino metabolites. Over a 1-year period within the city limits of Paris and three suburbs, we tested blood and urine from victims of sexual assaults, robbery and battery in which psychoactive substances were suspected of being involved. Hair was collected 4–8 weeks after the alleged DFC. Over the 128 cases studied, results of simultaneous analysis of blood, urine, and hair allowed us to conclude that 23 cases were real DFC. In 18 cases, no conclusion was possible since no hair was sampled and/or results were negative. In 56 cases, victims were previously using narcotics, cannabis, and/or a prescribed drug, according to the compounds detected in hair strands. Thirty-one cases were not DFC cases. This study indicates that the prevalence of zolpidem and clonazepam is high, followed by bromazepam, nordazepam, and midazolam. Others benzodiazepines and analogs are rare. LC–ESI-MS/MS is a good tool for toxicological investigations of DFC. Testing blood, urine, and hair by this technique may reveal drug presence, even if it was administered at a single therapeutic dose. That may be helpful to prosecute perpretators or to exclude a drug-facilitated crime.
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