Publications by authors named "Laurie Gheddar"

18 Publications

  • Page 1 of 1

Testing for anabolic steroids in human nail clippings.

J Forensic Sci 2021 Apr 22. Epub 2021 Apr 22.

Institut de médecine légale, Strasbourg, France.

Anabolic steroids are synthetic derivatives of testosterone, and their abuse can have numerous health consequences. Identification of this group of drugs has found applications in forensic toxicology, clinical situations, psychiatric disorders, and of course, anti-doping violations. Although anabolic steroids are generally tested in urine and very occasionally in head hair, collectors can face the lack of standard specimens, and therefore, nail clippings can be the unique alternative choice. Although there is no possibility to perform segmental analyses using nail clippings, the window of drug detection is generally much longer in nail when compared to head hair (particularly in male subjects), that is, 3-8 months and 4-12 months for finger and toenail clippings, respectively. A new method was developed, including nail pulverization in a ball mill, sonication for 90 min in methanol, and a combination of liquid-liquid and solid-phase extractions, followed by gas and liquid chromatography coupled to tandem mass spectrometry. To document the application of steroid testing in nail clippings, the authors present 6 authentic cases of abuse, involving stanozolol (7 and 24 pg/mg), nandrolone (6 pg/mg), trenbolone (26, 67, 81, and 89 pg/mg), drostanolone (8 and 11 pg/mg), and testosterone enanthate (14 pg/mg). Given concentrations were always in the low pg/mg range, the use of tandem mass spectrometry appears as a prerequisite.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1556-4029.14729DOI Listing
April 2021

Analysis of pharmaceutical products and dietary supplements seized from the black market among bodybuilders.

Forensic Sci Int 2021 May 30;322:110771. Epub 2021 Mar 30.

Laboratoire de Pharmacologie - Toxicologie, Centre Hospitalier Universitaire Raymond Poincaré, FHU Sepsis, AP-HP, 104 boulevard Raymond Poincaré, 92380 Garches, France; Plateforme de Spectrométrie de Masse MassSpecLab, INSERM UMR 1173, UFR des Sciences de la Santé Simone Veil, Université Paris-Saclay (Versailles Saint-Quentin-en-Yvelines), 2 avenue de la source de la Bièvre, 78180 Montigny-le-Bretonneux, France. Electronic address:

Substandard/counterfeit drugs are a growing global problem. According to the World Health Organisation, counterfeit medicines are medicines that are mislabelled deliberately and fraudulently regarding their identity and/or source. In high income countries, drugs seized are mainly represented by performance and image enhancing drugs (PIEDs). The aim of this study was to present the qualitative and quantitative results of toxicological analyses of pharmaceutical and dietary supplements seized from the black market among bodybuilders in France. All dietary supplements and pharmaceuticals seized from the black market and addressed to the laboratory for a qualitative and quantitative analysis between January 2016 and December 2019 were included in the study. A screening was carried out by gas chromatography-mass spectrometry and liquid chromatography-high resolution mass spectrometry. Identified compounds were quantified by liquid chromatography-tandem mass spectrometry. One hundred and ten products were seized and submitted to the laboratory for identification of active compounds and quantification: 75 pharmaceuticals and 35 dietary supplements. This included 39 oily and 3 aqueous solutions for intramuscular injection, 34 tablets, 13 capsules, 14 powders, 4 liquids and 3 lyophilizates. Among the pharmaceuticals, 25/75 (33%) were substandard (dosage not on the acceptable range defined for original products), 24/75 (32%) were counterfeit (qualitative formulation does not match the label) and 14/75 (19%) were original (qualitative formulation and levels of active ingredients fully matches the declared formulation. The analysis of the 12 remaining products revealed a correct qualitative content for 11/75 (15%), but quantitation could not be carried out because of the lack of reference standards at the time of the analysis. Fifty-four pharmaceuticals contained anabolic-androgenic steroids (AAS). Four out of 54 (7.4%) AAS were found as original, 8/54 (15%) could not be quantified (one with wrong active ingredient), corresponding to 43/54 (80%) AAS being non-original. In contrast, only 1/35 dietary supplement (3%) was adulterated, with a doping substance (1,3-dimethylbutylamine, DMBA). This work allows to show that France is not spared by the trafficking of PIEDs. The use of counterfeit drugs in mainstream population is an underestimated public health issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.forsciint.2021.110771DOI Listing
May 2021

Anabolic steroids and extreme violence: a case of murder after chronic intake and under acute influence of metandienone and trenbolone.

Int J Legal Med 2021 Apr 4. Epub 2021 Apr 4.

Institut de Médecine Légale, 11 rue Humann, F-67000, Strasbourg, France.

A 32-year-old male went to the police to claim he just killed his girlfriend by inflicting several stabs with a kitchen knife. He was very nervous and particularly aggressive. About 90 min after the assault, a blood specimen was collected with natrium fluoride as preservative. The blood was free of alcohol, pharmaceuticals and drugs of abuse, but tested positive by LC-MS/MS for metandienone (32 ng/mL) and trenbolone (9 ng/mL). The perpetrator admitted regular consumption of anabolic steroids to enhance his muscular mass, as he was a professional security agent. To document long-term steroid abuse, a hair specimen was collected 3 weeks after the assault, which tested positive for both drugs. Segmental analyses revealed in the proximal 1.5 cm segment, corresponding to the period of the assault, the simultaneous presence of metandienone (11 pg/mg) and trenbolone (14 pg/mg), while only metandienone (3 pg/mg) was identified in the distal 1.5 cm segment. As aggressiveness and violence can be associated with abuse of anabolic steroids, the aetiology of this domestic crime was listed to be due impulsive behaviour in a context of antisocial lifestyle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00414-021-02587-yDOI Listing
April 2021

Simultaneous testing for anabolic steroids in human hair specimens collected from various anatomic locations has several advantages when compared with the standard head hair analysis.

Drug Test Anal 2021 Feb 25. Epub 2021 Feb 25.

Laboratory of Toxicology, Institut de medecine légale, Strasbourg, France.

Since the late 90s, hair testing for anabolic steroids in humans has found numerous forensic, clinical, and anti-doping applications. In most cases, analyses were performed on head hair, collected in the vertex regions. However, for various reasons (shaved subject, bald subject, religious belief, cosmetic treatment and aesthetic reason), hair collectors can face the lack of head hair, and therefore, body hair can be the unique alternative choice. Although there is no possibility to perform segmental analyses with body hair, their use has two major advantages: (1) In most cases, anabolic steroids are more concentrated in body hair when compared with head hair, which allows detecting abuse at lower frequency and for lower dosages; and (2) the window of drug detection is generally much longer in body hair when compared with head hair, particularly in male athlete presenting short head hair. To document the relevance of simultaneous collection of head and body hair, the authors present eight authentic cases of anabolic steroids abuse, including clostebol (one case), drostanolone (one case), metandienone (one case), 19-norandrostenedione (one case), stanozolol (two cases) and trenbolone (three cases). In all cases, body hair concentrations were higher than head hair concentrations. Even in three cases, no steroid was identified in head hair, although present in body hair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.3020DOI Listing
February 2021

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

Forensic Sci Res 2020 Jan 29;5(4):322-326. Epub 2020 Jan 29.

Institut de Médecine Légale, Laboratoire de toxicologie, Strasbourg, France.

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 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 possession 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 13.9 ng/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 10 days after administration. The analysis of this specimen highlighted the presence of adrafinil at 0.8 ng/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 consumption of adrafinil, in accordance with abuse of modafinil alone. Intelligence considered that this was a trafficking case of adrafinil, with no self-consumption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20961790.2019.1704482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782130PMC
January 2020

Characterization of letrozole in human hair using LC-MS/MS and confirmation by LC-HRMS: Application to a doping case.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jan 15;1162:122495. Epub 2020 Dec 15.

Institut de médecine légale, 11 rue Humann, 67000 Strasbourg, France; X-Pertise Consulting, 42 rue Principale, 67206 Mittelhausbergen, France.

Letrozole is a reversible aromatase inhibitor, used in the treatment of hormone-dependent woman cancer. No indication for medical use is available for men. In recent years, several cases of doping with letrozole have been observed, especially among high level athletes. Aromatase inhibitors reverse the harmful effects (feminizing) of the abuse of anabolic androgenic steroids. Letrozole is included on the list of products prohibited in- and out-competition by the World Anti-Doping Agency, under section S4.1. The aim of the present work was to develop a specific method to identify letrozole in human hair of a male amateur athlete by LC-MS/MS and confirmation by LC-HRMS, after incubation of 20 mg of matrix in 1 mL of methanol. The chromatographic separation was performed using a reverse phase column HSS C18 with a gradient elution of 15 min (from 87% to 5% of formate buffer adjusted to pH 3). Linearity was observed from 1 to 1000 pg/mg (r = 0.9999), after spiking blank hair with the corresponding amounts of letrozole. The limit of detection was estimated at 0.5 pg/mg and the lower limit of quantification was the first point of the calibration curve, i.e. 1 pg/mg. The precision was lower than 20% and there was no interference with the analytes by chemicals or any extractable endogenous materials present in hair. Letrozole was identified in the male amateur athlete hair at 310 pg/mg (segment 0-2 cm) and 245 pg/mg (segment 2-4 cm).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2020.122495DOI Listing
January 2021

Perspectives in Evaluating Selective Androgen Receptor Modulators in Human Hair: A Short Communication.

Ther Drug Monit 2021 04;43(2):298-300

Institut de Médecine Légale, University of Strasbourg, Strasbourg, France.

Background: As hair testing increases the window of drug detection and permits the differentiation of long-term use from a single exposure when performing segmental analyses (which also allows establishing the pattern of use), this matrix should be considered as a suitable complement to standard investigations in clinical, forensic, and sport toxicology. The authors were recently involved in 3 cases where hair analysis was used to demonstrate the use of selective androgen receptor modulators (SARMs), including ligandrol (LGD-4033), andarine (S-4), and ostarine (S-22). SARMs are increasingly being abused as "safe" alternatives to steroids.

Methods: After decontamination using dichloromethane, hair specimens were segmented, cut into very small segments (<1 mm), incubated overnight in a buffer, and extracted using a mixture of organic solvents. Drugs were tested using liquid chromatography-tandem mass spectrometry and confirmed using liquid chromatography/HRMS.

Results: The determined concentrations were as follows: ligandrol, 14-42 pg/mg; andarine, 0.1-0.7 pg/mg; and ostarine, 3-21 pg/mg.

Conclusions: To enhance performance, SARMs must be used on a long-term basis, which can have serious clinical consequences, including liver damage, myocardial infarction, and blood clots. Hair testing for SARMs has additional benefits versus urine analysis as it can detect the parent compound and numerous metabolites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FTD.0000000000000859DOI Listing
April 2021

Analysis of Cocaine and its Metabolites in Urine After Consummation of Coca Tea by Five Subjects and Subsequent Hair Testing.

J Anal Toxicol 2020 Dec 5. Epub 2020 Dec 5.

Institut de Médecine Légale, Strasbourg, France.

Coca tea is a popular drink in some South American countries where it is reputed to have medicinal properties. This preparation is composed of natural cocaine alkaloids and therefore can be banned in some countries. During an anti-doping control in Peru, the urine of an athlete tested positive for benzoylecgonine, ecgonine methyl ester and cocaine (400 ng/mL, 180 ng/mL and 0.5 ng/mL, respectively). The athlete indicated that she had consumed a coca tea in the morning before the competition. As her lawyer contacted us to assess the scientific aspects of possible involvement of coca tea to explain the adverse analytical finding, a study was implemented with the same tea bags. Five volunteers from the laboratory consumed 250 mL of coca tea containing approximately 3.8 mg of cocaine. Urine (11 specimens for each subject) was collected over 3 days to follow the elimination of cocaine and metabolites (benzoylecgonine and ecgonine methyl ester). All samples were analyzed by UHPLC-MS/MS after alkaline extraction. Cocaine was identified for 20 hours, with concentrations ranging from 6 to 91 ng/mL. Benzoylecgonine and ecgonine methyl ester were identified for 70 hours and for 60 hours, respectively, with concentrations ranging from 6 to 3730 ng/mL and from 6 to 1738 ng/mL. The concentration profiles were identical for the five volunteers. This study supports the athlete's claims. In addition, the hair of the five subjects was collected a month later and all the hair tests were negative for cocaine using a limit of decision at 10 pg/mg. Although it is accepted that a 4 mg dose of cocaine has no significant pharmacological effect, the consummation of coca tea can lead to significant legal consequences since the measured urine concentrations sometimes cannot be considered incidental. Therefore, discrimination between coca tea consummation and recreational cocaine abuse relies primarily on hair analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkaa190DOI Listing
December 2020

Identification of furosemide in hair in a post-mortem case by UHPLC-MS/MS with guidance on interpretation.

J Forensic Sci 2021 Jan 7;66(1):272-277. Epub 2020 Oct 7.

Institut de Médecine Légale, Strasbourg, France.

Testing for drugs in hair raises several difficulties. Among them is the interpretation of the final concentration(s). In a post-mortem case, analyses revealed the presence of furosemide (12 ng/mL) in femoral blood, although it was not part of the victim's treatment. The prosecutor requested our laboratory to undertake an additional analysis in hair to obtain information about the use of furosemide. A specific method was therefore developed and validated to identify and quantify furosemide in hair by UHPLC-MS/MS. After decontamination of 30 mg of hair, incubation in acidic condition, extraction with ethyl acetate, the samples were analyzed by UHPLC-MS/MS. Furosemide was found in the victim's hair at 225 pg/mg. However, it was not possible to interpret this concentration due to the absence of data in the literature. Therefore, the authors performed a controlled study in two parts. In order to establish the basis of interpretation, several volunteers were tested (four after a single 20 mg administration and twenty-four under daily treatment). The first part indicated that a single dose is not detectable in hair using our method. The second part demonstrated concentrations ranging from 5 to 1110 pg/mg with no correlation between dosage and hair concentrations. The decedent's hair result was interpreted as repeated exposures. In the case of furosemide analysis, hair can provide information about its presence but cannot give information about dosage or frequency of use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1556-4029.14585DOI Listing
January 2021

Identification of S22 (ostarine) in human nails and hair using LC-HRMS. Application to two authentic cases.

Drug Test Anal 2020 Oct 14;12(10):1508-1513. Epub 2020 Aug 14.

Institut de médecine légale, 11 rue Humann, Strasbourg, F-67000, France.

Ostarine, also known as S22 or MK2866 and enobosarm, is a selective androgen receptor modulator (SARM). It has high anabolic potency, in addition to limited androgenic effects. At this time, ostarine has no therapeutic use, but can be abused for performance-enhancing purposes using the oral route, at dosages of 10-25 mg per day. As the drug can easily be obtained via the Internet or some fitness centers, athletes and more and more amateurs can use it without undergoing the deleterious physiological side effects that are generally associated with testosterone-related compounds. Since 2008, the World Anti-Doping Agency (WADA) has prohibited SARMs at-all-times in the category of "other anabolic agents" under section S1.2 of the WADA List. In a case of trafficking/abuse, ostarine was identified in nail (subject 1) and hair (subject 2) by LC/HRMS after incubation of 50 mg of matrix in a pH 9.5 buffer, followed by extraction with organic solvents. The drug was quantitated by LC-MS/MS. Ostarine tested positive at 61 pg/mg (toenails) and 111 pg/mg (fingernails) for subject 1. Ostarine was present at 146, 168, 93, and 101 pg/mg in the 4 × 3 cm hair sections of subject 2, clearly demonstrating long-term use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.2902DOI Listing
October 2020

Cocaine External Contamination Can Be Documented by a Hair Test.

J Anal Toxicol 2021 Jan;44(9):e4-e5

Institut de medecine légale, 11 rue Humann, Strasbourg F-67000, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkaa061DOI Listing
January 2021

Testing for GW501516 (cardarine) in human hair using LC/MS-MS and confirmation by LC/HRMS.

Drug Test Anal 2020 Jul 25;12(7):980-986. Epub 2020 Apr 25.

Institut de medecine légale, Strasbourg, France.

GW501516, also known as GW-1516 or cardarine and endurobol, is a peroxisome proliferator-activated receptor delta (PPAR-δ) agonist. Activation of the receptor will increase fat-burning capacity and muscle production, as it changes the body's fuel preference from glucose to lipids. GW501516 has no therapeutic use, but can be abused for performance-enhancing purposes using the oral route, at dosages of 10 to 20 mg per day, for 6 to 8 weeks. Both athletes and amateurs can abuse GW501516 as the drug can be easily obtained via the Internet. Since January 2009, the list of prohibited substances and methods of doping as established by the World Anti-Doping Agency includes GW-501516, first as a gene doping substance and now in the S4.5 Metabolic modulators class. It is prohibited at all times. Using LC/MS-MS and confirmation by LC/HRM, after methanol incubation of 20 mg with ultrasound for 1 hour, GW501516 was identified in the hair of a male abuser at 32 and 22 pg/mg in 2 × 2 cm segments. The result is the first evidence that this compound with a carboxylic acid function is incorporated in human hair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.2802DOI Listing
July 2020

Testing for Stanozolol, Using UPLC-MS-MS and Confirmation by UPLC-q-TOF-MS, in Hair Specimens Collected from Five Different Anatomical Regions.

J Anal Toxicol 2020 Dec;44(8):834-839

Institut de Médecine Légale, 11 rue Humann, Strasbourg 67000, France.

An athlete challenged the result from an in-competition doping test which returned with an adverse analytical finding for stanozolol, claiming it was due to supplement contamination. Her lawyer asked the laboratory to analyze several hair specimens simultaneously collected from five different anatomical regions, head, arm, leg, pubis and armpit, to document the pattern of drug exposure. A specific UPLC-MS-MS method was developed. After decontamination with dichloromethane, stanozolol was extracted from hair in the presence of stanozolol-d3 used as internal standard, under alkaline conditions, with diethyl ether. Linearity was observed for concentrations ranging from 5 pg/mg to 10 ng/mg. The method has been validated according to linearity, precision and matrix effect. Concentrations of stanozolol in head hair, pubic hair, arm hair, leg hair and axillary hair were 73, 454, 238, 244 and 7,100 pg/mg, respectively. The concentration of stanozolol in head hair is in accordance with data published in the literature. When comparing the concentrations, body hair concentrations were higher than the concentration found in head hair. These results are consistent with a better incorporation rate of stanozolol in body hair when compared to head hair. The simultaneous positive concentrations in different hair types confirm the adverse analytical finding in urine of the top athlete, as the measured concentrations do not support the theory of contamination. For the first time, an anabolic agent was simultaneously tested in hair collected from five different anatomical regions from the same subject, with a large distribution of concentrations, due to anatomical variations, and these findings will help interpretation in further doping cases when documented with hair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkaa023DOI Listing
December 2020

Hair testing for doping agents. What is known and what remains to do.

Drug Test Anal 2020 Mar 29;12(3):316-322. Epub 2020 Jan 29.

Institut de médecine légale, 11 rue Humann, F-67000, Strasbourg, France.

Hair testing is a complementary approach to document doping agent(s) use All prohibited substances but hormones should be detectable in hair Interest and limitations of hair testing for doping agents are reviewed based on the authors' experience Although a lot of data are available for drugs of abuse, controlled studies are missing for anabolic steroids, diuretics and some unusual classes of substances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.2766DOI Listing
March 2020

Complete Post-mortem Investigations in a Death Involving Clenbuterol After Long-term Abuse.

J Anal Toxicol 2019 Sep;43(8):660-665

Institut de Médecine Légale, 11 Rue Humann, F-67000 Strasbourg, France.

The body of a 61-year-old man was found at his home by his wife, lying on the floor, near the bathroom, around midnight. He was known to be training for bodybuilding, using anabolic steroids. Police investigations revealed the presence of two types of tablets at home, one supposed to contain clenbuterol (0.040 mg) and the other stanozolol (10 mg). Testing the tablets revealed different dosages from what was expected, i.e., 0.073 and 11.5 mg/tablet, for clenbuterol and stanozolol, respectively. External body examination and autopsy, which was performed the next day, revealed generalized organ congestion and lack of any traumatic injury (confirmed by radiology). Cardiomegaly, with a heart weighing 692 g, was obvious. Anatomic pathology tests did not reveal evidence of malformations, but atheromatous plaque was identified in the coronaries during complete histology investigations. Femoral blood, urine, bile, gastric contents and two strands of hair (6 cm) were collected for toxicology. These specimens were submitted to standard analyses, but also to a specific LC-MS-MS method for clenbuterol and stanozolol testing. Clenbuterol was identified in all the tissues, including femoral blood (1.1 ng/mL), urine (7.2 ng/mL), bile (2.4 ng/mL), gastric content (3.2 ng/mL) and hair (23 pg/mg). Stanozolol only tested positive in hair (11 pg/mg). All other analyses were negative, including blood alcohol and drugs of abuse. The pathologists concluded to cardiac insufficiency with support of cardiomegaly, in a context involving repetitive abuse of anabolic drugs. This case indicates that more attention should be paid to clenbuterol, a drug widely used as a stimulant by people who want to lose weight, athletes and bodybuilding practitioners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkz058DOI Listing
September 2019

Testing for Betel Nut Alkaloids in Hair of Papuans Abusers using UPLC-MS/MS and UPLC-Q-Tof-MS.

J Anal Toxicol 2020 Jan;44(1):41-48

Institut de Médecine Légale, 11 rue Humann, F-67000 Strasbourg, France.

Betel nut is the fruit of Areca palm, growing in Papua New Guinea. Mixed with limestone and stick mustard, arecoline and guvacoline, which are present in betel nut, are hydrolyzed into arecaidine and guvacine, respectively. As part of the study on dietary habits of Papuans residents, our laboratory was asked to analyze the four alkaloids in hair to document long-term exposure. Hair samples were collected from 19 adult subjects (males = 11; females = 8), by some of the authors, and were sent to the laboratory for analysis. The four alkaloids have very similar chemical structures. In order to accurately identify the drugs, two methods were developed. First, the compounds were identified using an ultra-high-performance liquid chromatography system coupled to time-of-flight mass spectrometry. Then, they were quantified by an ultra-high-performance liquid chromatography system coupled to tandem mass spectrometry. After decontamination with dichloromethane, hair samples were cut into very small segments and 20 mg were incubated in methanol for 2 h 30 min in an ultrasound bath. After cooling, the methanol was evaporated to dryness in presence of 20-μL octanol to prevent volatilization. Nicotine-d4 was used as an internal standard. Linearity was observed for concentrations ranging from the limit of quantification to 20 ng/mg for arecoline, arecaidine, guvacine and guvacoline. Measured concentrations were in the range 60 pg/mg to 18 ng/mg for arecoline (n = 19), 14 pg/mg to 2.5 ng/mg for guvacoline (n = 11), 63 pg/mg to 3.8 ng/mg for arecaidine (n = 11) and 100 pg/mg to 3.2 ng/mg for guvacine (n = 6). There was no correlation between concentrations of arecoline and arecaidine (ratio from 0.01 to 0.18) and guvacoline and guvacine (ratio from 0.06 to 3.50). However, the identification of these substances in hair is a good marker of consumption of betel nut and allows us to document a local practice that remains difficult to evaluate just by questioning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jat/bkz045DOI Listing
January 2020

Identification and analytical characterization of seven NPS, by combination of H NMR spectroscopy, GC-MS and UPLC-MS/MS, to resolve a complex toxicological fatal case.

Forensic Sci Int 2019 May 9;298:140-148. Epub 2019 Mar 9.

Institut de Médecine Légale, Université de Strasbourg, 67085 Strasbourg, France; X-Pertise Consulting, 84 Route de Saverne, F-67205 Oberhausbergen, France.

The authors report the case of a 41-year-old man known as a polydrug addict and found dead at home. The initial toxicological screening was inconclusive for a toxic death. However, 7 small bags of unknown powders and crystals, supposed to be NPS, were found near the body and sent to the laboratory 3 weeks later. This article focuses on the interest of nuclear magnetic resonance (NMR) spectroscopy to solve this fatal case. The 7 items were identified by H NMR and their purities were measured by the quantitative NMR (qNMR) method using maleic acid as internal standard. The compounds were 4-chloro-α-pyrrolidinopentiophenone, dibutylone, 4-chloroethcathinone, 4-α-pyrrolidinohexuiphenone, 3,4-methylenedioxy-N-benzylcathinone, 3-methoxy-phencyclidine and α-pyrrolidinopropiophenone, with purities in the range 51-89%. In the biological specimens of the victim, only 3-methoxy-phencyclidine (3-MeO-PCP) was identified in cardiac blood, peripheral blood and urine at 743, 489 and 16,700 ng/mL. Hair (6 cm) concentration of the drug was 15,600 pg/mg. The other NPS were not detected. The peripheral blood concentration was higher than the values reported in previous intoxicated and fatal cases. The toxicological significance of the measured concentration in hair was difficult to establish because this is only the second case describing a test result for 3-MeO-PCP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.forsciint.2019.03.003DOI Listing
May 2019

Interpretation of Cannabis Findings in the Hair of Very Young Children: Mission Impossible.

Curr Pharm Biotechnol 2017 ;18(10):791-795

Institut de Medecine legale, 11 rue Humann, 67000 Strasbourg, France.

Background: Hair has been suggested since the middle of the 90's to be a suitable matrix to document repetitive exposure to cannabis. Because it is possible to detect Δ9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) in cannabis smoke, the identification of the metabolite, 11-nor-Δ9-tetrahydrocannabinol carboxylic acid (THC-COOH) has been considered to allow the discrimination of active use.

Objective: Although the identification of an active compound in a child's hair shows contamination of the local environment, it is a challenge to discriminate between hair incorporation after ingestion or inhalation and environmental external deposition from dust, smoke, or even contaminated surfaces by hand contact. However, it is particularly important in case of children to correctly interpret the data, particularly for a realistic assessment of the health risk. We present here a series of hair tests for cannabis where the interpretation was almost impossible to establish.

Method: Hair specimens were collected during the autopsy of the 12 children, aged 2 to 24 months, either deceased from shaken baby syndrome (SBS, n=4), mechanic asphyxia (MA, n=1) or sudden infant death (SID, n=7) during January 2015 to April 2017. After decontamination, the hair specimens were tested for THC, CBN and CBD and THC-COOH. The whole length of hair was submitted to analysis.

Results: The amount of hair from children can be as low as 8 mg. This may affect the limit of quantitation of all drugs, but particularly THC-COOH. Eight from twelve hair tests were positive for cannabis markers, i.e. THC (39 to 1890 pg/mg, n=8), CBN (< 5 to 1300 pg/mg n=8), CBD (10 to 2300 pg/mg, n=8) and THC-COOH (not detected to < 0.5 pg/mg, n=5). In 4 cases from 8 positive findings, it was not possible to test for THC-COOH (not enough material).

Conclusion: Establishing a window of detection when testing for drugs in young children is a very complicated task. Hair from children is finer and more porous in comparison with adult (the risk of contamination from sweat and environmental smoke is higher than in adults). The final interpretation of cannabinoid findings in the children's hair is very complicated as this can result from in utero exposure (although none of the mother admitted cannabis use during pregnancy), oral cannabis administration by the parents to achieve sedation, close contact to cannabis consumers (hands, bedding, dishes) and inhalation of side-stream smoke. Over-interpreting cannabis findings in hair can have very serious legal implication in child protection cases. Practicing scientists have the responsibility to inform the child protection authorities, courts, etc. about these limitations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389201019666171129180206DOI Listing
May 2018