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Cet article rapporte le bilan de deux annees d'analyses de produits de saisies consecutives a la decouverte du “pot belge”, un produit dopant largement utilise dans le monde sportif, et en particulier dans le milieu du cyclisme. Cette pratique, qui existe depuis le debut des annees 1980, consiste a s'injecter en intramusculaire 0,5 ml de “pot belge”, avant, puis pendant la competition. Les analyses ont ete realisees par chromatographic gazeuse couplee a la spectrometrie de masse, par chromatographic liquide haute performance avec detection a barrette de diodes et par chromatographic liquide couplee a la spectrometrie de masse. Cinq types differents de “pot belge” ont ainsi pu etre identifies. La caracteristique commune consistait en une tres forte concentration d'amphetamine (14 a 52 mg/ml). Selon les echantillons, elle etait associee a tout ou partie des substances suivantes : heroine (12,5 μg/ml), cocaine (2,3 a 9 μg/ml), ethanol, acide acetylsalicylique, carbasalate calcique, phenacetine, ethenzamide, butanamides et cafeine. Les auteurs rapportent les circonstances dans lesquelles les sportifs peuvent etre amenes a utiliser ce moyen de dopage, ainsi que les risques engendres par une telle pratique compte tenu des concentrations observees pour chacun de ces produits.

L'augmentation des teneurs en THC dans les produits a base de cannabis vendus en France est, depuis quelques annees, frequemment evoquee dans la litterature. Cependant, a notre connaissance, cette affirmation ne repose sur aucune base bibliographique. L'objet de la presente etude a ete de verifier la valeur de cette information. Nous avons rassemble 5152 resultats d'analyses obtenus de 1993 a 2000 sur des produits de saisies effectuees par les services des douanes, de la police nationale et de la gendarmerie nationale. Les renseignements fournis indiquaient l'annee de la saisie, le type de produit et la teneur observee en delta-9 tetrahydrocannabinol (THC). Les analyses etaient realisees par chromatographie en phase gazeuse couplee a la spectrometrie de masse. Les resultats indiquent que, quelle que soit l'annee etudiee, une tres grande variabilite des concentrations etait observee pour “l'herbe” mais aussi pour la “resine”. Des concentrations en THC inferieures a 2 % etaient relativement frequentes (18 % des echantillons). Jusqu'en 1995, 75 % des echantillons d'herbe contenaient moins de 5,5 % de THC, et la teneur la plus elevee observee dans une saisie a ete de 8,7 %. Pendant la meme periode, 47 % des echantillons de resine contenaient entre 5 et 10 % de THC. Depuis 1996, bien que d'une facon generale les teneurs observees dans la majorite des echantillons n'aient pas beaucoup evolue (54% des echantillons d'herbe et 71 % des echantillons de resine contenaient respectivement moins de 5 % et moins de 10 % de THC), sont apparus de facon exceptionnelle des echantillons a base de cannabis tres fortement concentres en THC. Au cours de l'annee 2000, 3 % des echantillons d'herbe et 18 % des echantillons de resine analyses contenaient plus de 15 % de THC. Ces echantillons tres concentres correspondaient le plus souvent aux nouveaux produits comme la “skunk”, la “super skunk” ou le “pollen”. En conclusion, il y a eu depuis 1996 une augmentation des teneurs en THC avec notamment l'apparition de nouveaux produits tres fortement titres, mais cette evolution n'a concerne qu 'une minorite des echantillons disponibles sur le marche clandestin francais.

Les proprietes sedatives et anxiolytiques du principe psychoactif principal du cannabis, le delta-9 tetrahydrocannabinol (THC), sont connues depuis des millenaires. Cette connaissance empirique a ete confirmee ces dernieres annees par une meilleure comprehension des mecanismes d'action du THC. Au niveau neuronal, il induit une diminution intracellulaire du potassium et une augmentation du calcium. Ceci se traduit par une alteration des capacites d'exocytose de certains neurotransmetteurs, dont le glutamate. Par ailleurs, il est desormais bien etabli que les zones du cerveau dans lesquelles le THC exerce ces effets sont les memes que celles ou agissent les medicaments sedatifs et les betabloquants, substances egalement utilisees dans la pratique du dopage. Les proprietes sedatives du cannabis sont recherchees par les athletes, les jours precedant les competitions pour favoriser l'endormissement, un souci majeur pour ces sportifs de haut niveau. Dans les disciplines sportives necessitant un etat de relaxation important au cours de la competition, ce qui est le cas pour tous les sports d'adresse (tir, equitation, etc.), les proprietes anxiolytiques du cannabis sont egalement tres attractives. En consequence, et bien que le cannabis puisse etre responsable d'une diminution des performances biomecaniques, il est utilise par les sportifs de haut niveau pour son aptitude a ameliorer les performances psychologiques ; il est donc logique qu'il soit proscrit au meme titre que certaines classes de medicaments destines a se substituer aux methodes naturelles de preparation psychologique.

Chez l'enfant avant l'âge de 12 ans, les intoxications constituent la deuxieme cause d'accident a domicile apres les traumatismes (1). Elles sont caracterisees par leur grande frequence et leur habituelle benignite. Avant l'âge de 6 ans, la benignite est habituelle ceci s'explique par le caractere accidentel, la faible quantite ingeree, la presence des parents et une consultation medicale rapide. En France, en 1994, on a rapporte 6 deces par divers produits et 9 par le monoxyde de carbone sur les 878 cas d'accidents domestiques dans la tranche d'âge 0-19 ans (2). La strategie de prise en charge des intoxications aigues de l'enfant doit tenir compte des donnees epidemiologiques, differentes de celles des adultes et variable selon l'âge. Elle doit aussi tenir compte des variabilites physiologiques, absorption, metabolisme et excretion, susceptibles de modifier la cinetique des xenobiotiques (3, 4). Epidemiologic La majorite des intoxications concerne l'enfant : 1,08 millions de cas d'ingestion de substances toxiques ont ete rapportes en 1998 par les centres antipoison (CAP) americains chez les enfants de moins de 6 ans (5). La proportion des incidents toxiques, rapportes aux CAP americains est estimee a moins de 26 %, suggerant un nombre de plus de 4 millions d'intoxications par annee aux USA (6). Environ 85 000 jeunes enfants ont ete traites pour intoxication aigue en 1998, dans des services d'urgence americains (7). En 1996 les CAP americains rapportaient sur 2,16 millions de cas d'intoxications 59,6 % chez des enfants de moins de 12 ans et 67,1 % des sujets de moins de 20 ans. Les intoxications medicamenteuses representaient 42 % des appels (5). En France avec environ 100 000 cas par an (8), les intoxications representent la deuxieme cause d'accident

Resume Le Guide de bonne execution des analyses (GBEA) en biologie medicale est opposable depuis le 4 decembre 1994 a l'ensemble des laboratoires tant prives que publics. Ce travail a pour but d'analyser cet arrete du 2 novembre 1994 en detaillant les douze domaines dans lesquels le biologiste doit apporter son analyse sur la demarche qualite, puis presenter une contribution a travers l'experience acquise dans un laboratoire de biologie d'un centre hospitalier. Enfin, un certain nombre d'analyses et de reflexions sont discutees en raison de l'impact economique et informatique induit par la mise en place du GBEA.

Cannabis is by far the most widely used drug of abuse in the world. Thus, it is not surprising to find THC or its metabolites in biological samples taken from victims of drug-facilitated crimes. Cannabis can be administered surreptitiously in pastries but those cases are rare. Like alcohol, most of the time cannabis is used by the offender and shared with the “agreement” of the victim resulting in what is called incapacitated rape or crime. Some of the psychoactive effects of THC such as euphoria, drowsiness, visual disorders and short memory troubles are expected by the perpetrator to facilitate the crime. This chapter emphasizes the role of cannabis in drug-facilitated or incapacitated crime situations with details on the products that can be used, the metabolism, the effects of cannabis and the interpretation of toxicological analysis.

Objectif Determiner la prevalence de l’usage d’alcool et de stupefiants chez des conducteurs d’automobiles decedes dans un accident de la circulation en France en 2014 et 2015, et de comparer les resultats obtenus avec ceux des periodes 2003–2004 [1] et 2010–2011 [2] selon le meme protocole (memes categories d’âge et memes seuils de positivite). Methodes Ont ete inclus les conducteurs decedes dans un accident de la circulation dans 14 departements du grand Sud-Ouest et du Nord-Est de la France. Le dosage de l’alcool dans le sang etait effectue par HS/CG-DIF, celui du THC et de ses metabolites par CG-SM tandis que la CL-SM-MS etait utilisee pour les amphetamines, la cocaine et les opiaces. Les seuils de positivite utilises sont ceux preconises par le consensus de la SFTA (en ng/mL) : THC = 0,5 ; 11-OH-THC = 0,5 ; THC-COOH = 2 ; morphine = 5 ; amphetamines = 10 ; cocaine et metabolites = 10. Une analyse en fonction de l’âge a egalement ete effectuee [1] , [2] . Resultats Au total, 359 conducteurs decedes, pour lesquels les resultats sanguins des 4 familles de stupefiants et de l’alcoolemie etaient disponibles, ont ete inclus dans l’etude. Les resultats concernant l’alcool (seuil de positivite 0,2 g/L) et le cannabis sont presentes dans le Tableau 1 . Le cannabis etait le stupefiant le plus frequemment retrouve, avec 32 % de sujets de moins de 30 ans sous influence au moment de l’accident. Cette valeur est tres superieure a celle qui avait ete trouvee dans l’etude realisee en 2010–2011 (22 %) sur un protocole identique [1] . En revanche, nous observons ici un score proche de celui qui avait ete observe pour le THC (29 %) pendant la periode 2003–2004, avec une cohorte de 2003 conducteurs [2] . Les prevalences d’usage des autres stupefiants pour les 359 conducteurs decedes etaient tres faibles, avec 1,7 % pour la morphine, 0,8 % pour les amphetamines ainsi que pour la cocaine. Avec 40 % de conducteurs alcoolises chez les moins de 30 ans, nous obtenons ici un score tres largement superieur a celui qui avait ete observe dans les etudes de prevalences precedentes pour cette tranche d’âge. Pour les conducteurs alcoolises, la distribution est d’allure gaussienne et 73 % d’entre eux presentaient une alcoolemie superieure a 1,5 g/L au moment de l’accident. Conclusion Les resultats de cette etude revelent principalement que l’alcool et le cannabis sont tres largement concernes dans la genese des accidents mortels de la circulation en France. Apres avoir mis en evidence une tendance a la baisse de la prevalence du cannabis chez les conducteurs decedes dans un accident de la voie publique entre 2004 et 2010, un inversement de cette tendance est aujourd’hui observe, dont les causes sont a determiner.

Sweat patches (n = 350) were collected throughout gestation from 29 opioid-dependent pregnant women participating in an outpatient methadone-assisted therapy program. Volunteers provided informed consent to participate in institutional review board-approved protocols. Methadone was eluted from sweat patches with sodium acetate buffer, followed by solid-phase extraction and quantification by gas chromatography mass spectrometry (limit of quantificationor = 10 ng/patch). Methadone was present in all weekly patches (n = 311) in concentrations ranging from 10.2 to 12,129.7 nanograms per patch and in 92.3% of short-term patches (n = 39, worn for 12 or 24 hours) in concentrations up to 3303.9 nanograms per patch. Correlation between patch concentrations and total amount of drug administered (r = 0.224), and concentrations and duration of patch wear (r = 0.129) were both weak. Although there were large intra- and intersubject variations in sweat drug concentrations, sweat testing was an effective alternative technique to qualitatively monitor illicit drug use and simultaneously document methadone medication-assisted treatment.

Chantier qualité GA This work was presented in part at the 14th Annual Meeting of the Société Française de Toxicologie Analytique, Le Touquet, France, 2006, and at the 44th International Meeting of the International Association of Forensic Toxicologists, Ljubljana, Slovenia, 2006.; International audience; To improve the knowledge of the postmortem redistribution of Δ9-tetrahydrocannabinol (THC), an animal model using the Large White pig has been developed, whereby 15 pigs received an intravenous injection of THC (200 µg/kg body weight) and were euthanized 2 h after administration. An autopsy was performed on three pigs immediately after being euthanized while the others were stored in supine position at ambient temperature for 6, 15, 24, or 48 h. THC concentration in blood from the vena cava decreased after death whereas left or right cardiac blood concentrations increased. No blood specimens collected from different sites of the carcasses adequately reflected the perimortem THC concentrations. The highest concentrations of THC at anytime were observed in lung tissue, and brain tissue seemed to present the most stable concentrations over time. This study can assist toxicologists in determining which specimens can, most appropriately, be used for interpretation of cannabinoid concentrations in postmortem specimens.

Resume En France comme de nombreux autres pays, le nombre des usagers de cannabis est en augmentation constante, et tout particulierement chez les jeunes. Avec les nouveaux produits, tres riches en principe actif, cette drogue possede une toxicite neuro-comportementale qui peut etre a l'origine de consequences graves pour l'individu et pour autrui. C'est pourquoi les cannabinoides sont de plus en plus souvent recherches et/ou doses, afin de depister et eventuellement quantifier l'impregnation de l'organisme. Les indications de ces recherches sont nombreuses, dont une nouvelle legislation sur la securite routiere qui institue un depistage systematique chez les conducteurs impliques dans un accident mortel. Le depistage rapide d'une consommation de cannabis peut etre realise dans l'urine par des methodes immunochimiques, parmi lesquelles existent desormais des tests sur « bandelettes a. Si leur sensibilite est suffisante dans la plupart des cas, il n'en va pas de meme pour la specificite et le nombre de resultats faussement positifs est loin d'etre negligeable. C'est pourquoi tout resultat positif doit imperativement etre confirme par une technique analytique specifique comme la chromatographie en phase gazeuse couplee a la spectrometrie de masse.

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.

Saliva or "oral fluid" has been presented as an alternative matrix to document drug use. The non-invasive collection of a saliva sample, which is relatively easy to perform and can be achieved under close supervision, is one of the most important benefits in a driving under the influence situation. Moreover, the presence of Delta9-tetrahydrocannabinol (THC) in oral fluid is a better indication of recent use than when 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) is detected in urine, so there is a higher probability that the subject is experiencing pharmacological effects at the time of sampling. In the first part of the study, 27 drug addicts were tested for the presence of THC using the OraLine IV s.a.t. device to establish the potential of this new on-site DOA detection technique. In parallel, oral fluid was collected with the Intercept DOA Oral Specimen Collection device and tested for THC by gas chromatography mass spectrometry (GC/MS) after methylation for THC (limit of quantification: 1 ng/mL). The OraLine device correctly identified nine saliva specimens positive for cannabis with THC concentrations ranging from 3 to 265 ng/mL, but remained negative in four other samples where low THC concentrations were detected by GC/MS (1-13 ng/mL). One false positive was noted. Secondly, two male subjects were screened in saliva using the OraLine and Intercept devices after consumption of a single cannabis cigarette containing 25mg of THC. Saliva was first tested with the OraLine device and then collected with the Intercept device for GC/MS confirmation. In one subject, the OraLine on-site test was positive for THC for 2 h following drug intake with THC concentrations decreasing from 196 to 16 ng/mL, while the test remained positive for 1.5 h for the second subject (THC concentrations ranging from 199 to 11 ng/mL). These preliminary results obtained with the OraLine IV s.a.t. device indicate more encouraging data for the detection of THC using on-site tests than previous evaluations.

A collaborative study was conducted in France in order to determine the prevalence of cannabinoids, opiates, cocaine metabolites and amphetamines in blood samples from drivers killed in road accidents in 2003 and 2004 and to compare these values with those of a previous study performed during the period 2000-2001 involving 900 drivers. Blood samples were provided from 2003 under 30-year-old drivers, killed in a traffic accident. Drugs of abuse were determined by gas chromatography-mass spectrometry using the same analytical procedures in all the 12 laboratories. The most frequently observed compounds were by far cannabinoids, that tested positive in 39.6% of the total number of samples. Delta9 tetrahydrocannabinol (THC), the most active of the principle constituents in marijuana (cannabis sativa), was detected in the blood of 28.9% drivers and was the single drug of abuse in 80.2% of the positive cases. It was associated with amphetamines in 7.4% and with opiates and cocaine in 1.9 and 4.8%, respectively. Amphetamines were present in 3.1% of the total number of samples, cocaine metabolites in 3.0% and opiates in 3.5%. When comparing these results with those of a previous study performed 3 years before, a significant increase is observed for THC (28.9% versus 16.9%), cocaine metabolites (3.0% versus 0.2%) and amphetamines (3.1% versus 1.4%). This study demonstrates the critical necessity of implementing in France as soon as possible systematical roadside testing for drugs of abuse.

L’augmentation constante du nombre des intoxications aigues, l’emergence de nouveaux problemes de sante publique comme le dopage du sportif, les affaires de soumission chimique ou la montee de la toxicomanie avec ses consequences sur l’insecurite routiere ont place les toxicologues analystes sur le devant de la scene. Dans le contexte hospitalier, si les technologies actuelles permettent potentiellement de resoudre tous les problemes, la collaboration etroite entre cliniciens et biologistes demeure primordiale tant au niveau local qu’au niveau des differentes societes savantes nationales, afin de mettre en synergie les competences des uns et des autres, pour une meilleure prise en charge therapeutique des patients.

Since 1958, many efforts have been made to fight against driving under the influence of alcohol. As a result of numerous studies, it appears that illicit drugs such as cannabis, cocaine, amphetamines and opiates are often involved in traffic accidents. Among biological media easily accessible, saliva is considered as the most suitable medium for revealing a recent use whereas blood is undoubtedly the only medium which can be used for confirmation and quantification. Reliable analytical methods are now available. So, all elements are gathered for undertaking a real prevention program, including drugs of abuse testing in drivers. In Germany, Sarland has set us an example with very frequent roadside drug testing, and such an action conduced to a very important decrease in the number of fatal and corporal road accidents in this country.

Introduction The interpretation Gamma-HydroxyButyric acid (GHB) concentrations in postmortem samples is a difficult task. Not only is GHB an endogenous substance, but it can also be produced in tissues after death and in vitro in stored samples. Collection of data from forensic cases is important in order to determine a possible threshold value enabling to differentiate between endogenous production and exogenous intake. As multiple analysis on different matrices are also helpful for the interpretation, we compiled a series of forensic cases where peripheral blood, cardiac blood and vitreous humor were analyzed. Methods 31 cases were selected, and analysis were carried out on all available matrices. Delay between death and sampling was unknown for most of the cases and the samples were kept at – 20°C before analysis. One case was a documented user of GHB. In the other cases no GHB intake was evoked in the circumstances of the death. The three matrices (vitreous humor, peripheral blood and cardiac blood) were present for 21 cases and for 10 other cases only two matrices were available (vitreous humor and peripheral blood). GHB was analyzed by gas chromatography- mass spectrometry (GC-MS) after derivation with BSTFA according to a previously published technique (Villain et al., 2003). The limit of quantification was 1 mg/L for all the matrices. Results 82 samples were analyzed, the results are presented in the table below: In peripheral blood, if only the matching pairs of blood samples were considered, mean concentration of GHB was 18,8 mg/L and median was 13,1 mg/L (N = 20). The ratios of the concentrations between the different matrices were evaluated and found as follows: [Cardiac blood]/[Peripheral blood] = 1.9 ; [Vitreous humor]/ [Peripheral Blood] = 0.4. Among the data presented, the alleged user of GHB had the highest concentration in vitreous humor (69 mg/L) and in peripheral blood (246 mg/L). Cardiac blood was not sampled in this case. The ratio between vitreous humor and peripheral blood for this documented abuse of GHB was 0.3. N Mean (mg/L) Median (mg/L) Range (mg/L) Peripheral blood 31 25.1 15.4 Cardiac blood 20 31.2 17.8 Vitreous humor 31 8.1 3.1 1.0 − 69.0 Conclusion Establishing a threshold value for differentiating endogenous production and exogenous intake of GHB is a complex goal. Numerous publications have given concentrations in various matrices. Most of the time the concentrations of GHB between cases with proven intake and cases where no GHB intoxication was suspected are overlapping. Delay between death and sampling, storage conditions and preservatives are some of the multiple factors that could influence the evolution of GHB concentrations over time. With our case series we have shown that the ratio between vitreous humor and peripheral blood is not different for subjects with no history of GHB abuse and intoxicated subjects. This finding needs to be confirmed on larger series of both positive and control cases.

A simple procedure for the determination of chlorophacinone in human serum by high-performance liquid chromatography is reported. After addition of a suitable internal standard, unknown samples were extracted at acid pH with ethyl acetate. The reconstituted methanolic extract was directly injected into the liquid chromatograph. Separation was performed with a Lichrospher C18 5-microns column with a methanol-phosphate buffer (85:15, v/v) mobile phase. The eluent was monitored with UV detection at 286 nm. The method was found to be sufficiently rapid, reproducible, selective, and sensitive for use in clinical and experimental pharmacokinetic studies. Application of this method to 20 intoxicated patients indicated that the risk of bleeding syndrome, which is always associated with this kind of intoxication, is no longer present when chlorophacinone levels drop to below 1 microgram/mL.

A rapid and specific method for the determination of iodide in urine by high-performance liquid chromatography on an anion-exchange column with electrochemical detection is described. The assay is reproducible as judged by the coefficient of variation of less than 4% at all concentrations used. The limit of detection was 0.1 μ mol, and the calibration graph was linear for concentrations between 0.1 and 200 μmol. Using this method, healthy volunteers were found to excrete 69±39 μmol of iodide per mole of creatinine.

An isocratic high-performance liquid chromatography method is described for the determination of Neopterine eliminated in human urine, using a μ-Bondapak C18 column (300 × 3.9 mm I.D.) and a strongly polar phosphate buffer (pH 6.2) for elution. This analysis requires only 15 minutes and allows very good reproduc-tibility of retention times. This method is well-suited for automation and routine clinical laboratory in order to quantify human urinary Neopterine in healthy subjects and in subjects with malignant disorders.

Summary Serial urinary neopterin determinations were performed in 151 patients after exeresis of a malignant melanoma. Values for patients clinically free of disease at the end of the observation were similar to those of healthy subjects. No significant varia tions were observed in patients with cutaneous meta stases. The most important variations were found in patients who developed ganglionic and above all visceral metastases. These data suggest that neopterin determination could be very useful in the follow-up of patients with a malignant melanoma and especially for detecting visceral metastases occurences.

A sensitive and specific determination of benzodiazepines in biological fluids is described, based on reversed-phase high-performance liquid chromatography. The compounds are extracted with a C2 AASP cartridge within 5 min. The recovery ranges from 92 to 104% and is independent of the concentration. Using a suitable gradient elution, complete separation of nineteen benzodiazepines is achieved in 50 min with detection limits of less than 3 ng/ml in urine and 5 ng/ml in other biological fluids. Using a rapid-scanning multichannel detector, the identities of the benzodiazepines can be confirmed. Prazepam is employed as internal standard. The precision and accuracy of the described method are suitable for monitoring benzodiazepine levels in clinical studies and an example is given.