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The value of hair in forensic toxicology has already been widely demonstrated. It offers a much wider detection window than other matrices, and its segmental analysis allows the documentation of a single, occasional or regular consumption of a large number of molecules. To date, considerable efforts are being made to achieve very high sensitivity using increasingly effective techniques in the forensic analysis of hair (gas chromatography with electron ionization mass spectrometry (GC--EI-MS); gas chromatography with chemical ionization mass spectrometry (GC--CI-MS); gas chromatography–tandem mass spectrometry (GC--MS-MS); high or ultra performance liquid chromatography–tandem mass spectrometry (HPLC–MS-MS and UPLC–MS-MS)). Since the early 2000s, work has been carried out to analyze hair using matrix-assisted laser desorption ionization (MALDI) coupled with imaging mass spectrometry (IMS). Intact, cut or pulverized, human head hairs are analyzed in all their forms. With a simplified and rapid sample preparation protocol, MALDI-IMS appears to be an attractive option for the forensic interpretation of hair analysis. The high spatial resolution clearly competes with conventional methods and strand segmentation. This article provides a complete overview on MALDI techniques used and its applications to better understand the pre-analytical and the analytical parts in the hair analysis.

Insulin aspart (NovoRapid®, NovoMix®, Novolog® and Fiasp®) is a fast-acting analog of human insulin, indicated in the treatment of type I and II diabetes. It is administered before meals to mimic the physiological insulin secretion that follows a rise in blood glucose. Its misuse for the purposes of suicide and murder and in the context of factitious order has often been described. In forensic medicine, the identification of insulin in biological samples has always been complex. In this paper, we present a case of suicide of a 64-year-old man who died after the injection of insulin aspart. He was suffering from terminal lung cancer and left a letter explaining the reasons for his suicide. Four empty NovoRapid® pens were found near the body. Body examination was unremarkable, and the femoral blood was collected in two dry Vacutainer™ tubes (red cap) and two sodium fluoride (NaF) tubes (gray cap). A liquid chromatography coupled to high-resolution mass spectrometry method was used to identify and discriminate insulin aspart from human insulin after immunopurification in the blood samples and in the pens. Blood specimens tested positive for insulin aspart with the concentrations of 36 and 37 ng/mL in dry tubes and 58 and 71 ng/mL in tubes containing NaF when tested ∼3 weeks after the collection of the specimens. The contents of the pens also matched with insulin aspart. The stability of insulin in blood is a critical point in the interpretation of the concentrations due to their rapid decrease caused by the activity of proteases in blood. During a degradation study implemented to compare three preservatives and dry tubes, suitable insulin aspart stability was observed with disodium salt of ethylenediaminetetracetic acid and NaF. Given that NaF is standard in forensic toxicology for measuring blood alcohol concentrations, the authors suggest its use for blood collection when insulin intoxication is suspected.

A 29-year-old man with no previous medical history was found dead at home. Anabolic products (tablets and oily solutions) and syringes were found at the scene. The man was known to train regularly at a fitness club and to use anabolic drugs. Following an unremarkable autopsy with normal histology, toxicological analyses were requested by the local prosecutor to provide further information. Blood, head hair (5 cm, black), body hair (axillary and leg) and toe and finger nail clippings were submitted to liquid and gas chromatography coupled to tandem mass spectrometry (LC and GC–MS-MS) methods to test for anabolic steroids. Blood tested positive for testosterone (4 ng/mL), boldenone (26 ng/mL), stanozolol (3 ng/mL) and trenbolone (

Resume Si la conquete de l’espace a marque la fin du millenaire precedant, la decouverte du monde aquatique est l’activite en plein essor depuis le debut des annees 2000. Au-dela de l’aspect economique du fait d’une richesse encore peu exploitee tant pour l’alimentation que pour les minerais, les mers et oceans sont des lieux fascinants qui attirent de plus en plus, a la surface (navigation) et sous l’eau (apnee, plongee). Ainsi, la plongee est devenue en quelques annees le sport incontournable a pratiquer. La notion de plongee loisir, developpee par l’organisme americain PADI (Professional Association of Diving Instructors), inclut des exigences precises en matiere de limites, de formation et d’equipement. Pour l’homme, il n’est pas possible de respirer sous l’eau sans un materiel adapte, qui doit aussi tenir compte des conditions environnementales, en particulier du froid. Du fait d’un nombre croissant de plongeurs certifies dans tous les pays du monde, il n’est pas surprenant que certains d’entre eux souffrent de pathologies diverses pendant leur activite. Il existe donc, pour la plongee, un certain nombre de contre-indications definitives, comme l’insuffisance cardiaque ou respiratoire, l’epilepsie ou des contre-indications temporaires. Parmi cette derniere categorie, la consommation de nombreux medicaments est repertorie comme a risque, comme les s-bloquants, les anti-arythmiques, certains antidiabetiques ou encore les anxiolytiques, les neuroleptiques et les antidepresseurs. Les auteurs rapportent un accident fatal de plongee chez une pratiquante reguliere (niveau 3) ou l’expertise toxicologique a mis en evidence du citalopram, un antidepresseur de type inhibiteur de la recapture de la serotonine, dose a 66 ng/mL, soit une concentration therapeutique. Une revue de la litterature, basee sur les bibliotheques classiques (PubMed, Web of science, Scopus) les sites de federations de plongee et les assureurs specifiques (DAN, AquaMed) a mis en evidence une pauvrete de l’information disponible, alors meme que les antidepresseurs, surtout de nouvelle generation, sont tres largement prescrits a la population generale.

Summary Selective androgen receptor modulators (SARMs) are a class of drugs presenting identical anabolic properties to usual anabolic steroids (testosterone, stanozolol, nandrolone…) in addition to marked reduced androgenic effects. These drugs have emerged in the doping area within the early 2000s. Ligandrol, ostarine, RAD-140 and andarine are the most popular agents belonging to this class. According to the world anti-doping agency (WADA) prohibited list, SARMs are prohibited at all times (i.e. in and out-of-competition) and are listed under the section S1.2 (other anabolic agents), a section that also contains clenbuterol. The compilation of the WADA testing figures reports from 2015 to 2019 has indicated a regular increase of adverse analytical findings (AAF) due to SARMs, particularly with ostarine and ligandrol. The implementation of highly sensitive chromatographic anti-doping analyses has induced high-profile challenges of anti-doping rules violations as athletes have claimed in numerous occasions that contamination was the reason for their AAF. As a result, hair tests were presented in order to establish the circumstances of these AAF. In case of an adverse analytical finding, hair testing can be a complement to document the claim of the athlete but of course, the result should not be considered as an alternative to urinalysis. This is because a negative hair result cannot exclude the use of the detected drug and cannot overrule the urine result. A review of the scientific literature, using the key words “SARMs” and “hair” has indicated that only 7 papers were published on this topic, including 3 dealing with equine hair. Although literature seems very limited, there is an increasing request for hair tests, which as prompted our laboratory to develop screening methods. Drugs are extracted from hair after decontamination under mild alkaline condition and submitted to LC-MS/MS and LC-HRMS assays. In this review, several original cases are provided, and the challenges of interpreting these findings are highlighted in light of the lack of controlled studies in the literature.

Objectifs En 2019, Salomone et al. [1] publiaient que la 4-anilino N-phenethyl-piperidine (4-ANPP), precurseur et metabolite de nombreux derives du fentanyl pouvait servir de marqueur d’exposition dans les cheveux a cette classe de molecules ultra-actives. Dans le cadre d’une intoxication fatale au fentanyl, les auteurs ont voulu verifier que la 4-ANPP pouvait egalement etre retrouvee dans d’autres matrices biologiques d’interet medicojudiciaire. En France et plus generalement en Europe, le fentanyl est moins frequemment responsable de deces qu’aux Etats-Unis et est principalement utilise comme analgesique chez les patients cancereux. Son usage detourne est surtout limite au personnel hospitalier, mais peut s’observer par diversion de patchs (Durogesic). Pour echapper aux regulations legales, le fentanyl fait partie des molecules les plus copiees et l’on retrouve, dans la grande famille des nouvelles substances psychoactives (NPS), plus d’une cinquantaine d’analogues, dont le carfentanil, le furanylfentanil ou encore l’ocfentanil. Face a cette proliferation et a la quasi-impossibilite pour un laboratoire de disposer de tous les standards de reference, la recherche ciblee de 4-ANPP semble etre un excellent moyen de depistage pour cette classe d’opioides. Methode Un homme de 36 ans est retrouve decede a son domicile, malgre l’intervention des services de secours. D’apres les temoins, l’individu aurait pu utiliser un patch de fentanyl en l’appliquant sous la langue. Il etait connu comme consommateur de produits stupefiants. Aucune cause traumatique de mort n’a pu etre constatee lors de l’autopsie et le Procureur de la Republique a requis une expertise toxicologique de reference a partir des prelevements classiques (sang femoral, sang cardiaque, urine, bile, contenu gastrique, cheveux noirs, de 4–5 cm, en vrac). Une methode analytique par UHPLC-MS/MS (Xevo TQD) permettant de doser le fentanyl et son metabolite primaire, le norfentanyl et d’identifier la 4-ANPP a ete utilisee. Tous les echantillons ont ete analyses apres une extraction par un melange ether diethylique/dichloromethane/hexane/alcool isoamylique (50/30/20/0,5) a pH 9,5, en presence de fentanyl-D5 et de norfentanyl-D5. Chaque compose a ete identifie par 2 transitions ioniques, dont m/z 281 > 188 et 281 > 105 pour le 4-ANPP. Seul le fentanyl et le norfentanyl ont ete quantifies, la caracterisation de la 4-ANPP etant uniquement qualitative au laboratoire (usage pour criblage). Resultats Le fentanyl a ete dose a 44 ng/mL dans le sang cardiaque et a 30 ng/mL dans le sang femoral, ce qui tend a demontrer une possible redistribution post-mortem avec un ratio de 1,5, la litterature retenant 1,6. Le norfentanyl est a 2 ng/mL dans les 2 echantillons de sang. On retrouve egalement le fentanyl et le norfentanyl dans les autres echantillons : urine (20 et 2 ng/mL), bile (112 et 10 ng/mL), contenu gastrique (101 et 1 ng/mL) et enfin cheveux (652 et 92 pg/mg). La 4-ANPP a ete retrouvee dans toutes les matrices biologiques et se revele donc etre un marqueur essentiel pour mettre en evidence une consommation de derives du fentanyl. Conclusion Les concentrations de fentanyl sont tres superieures aux concentrations therapeutiques usuelles et sont potentiellement letales par depression respiratoire, chez un sujet consommateur regulier de cette molecule. A ce jour, la police n’a pas identifiee la source du stupefiant. Les faibles concentrations de norfentanyl sont en faveur d’un deces rapide apres la consommation. Retrouvee dans toutes les matrices biologiques, la 4-ANPP confirme son statut de marqueur d’exposition aux derives du fentanyl. Quelques observations complementaires du laboratoire sur d’autres derives du fentanyl ont confirme cette approche, le concept etant qu’un criblage positif de la 4-ANPP donne lieu a des investigations tres poussees pour identifier la source.

Resume La scopolamine est le premier alcaloide a avoir ete commercialise sous la forme d’un systeme transdermique. Ce dispositif, commercialise sous la denomination Scopoderm®, a ete developpe pour delivrer de facon constante de la scopolamine a travers la peau, soit environ 5 μg/heure, pour traiter le mal des transports, les nausees recurrentes et l’encombrement des voies aeriennes superieures lie a l’exces de secretions salivaire. En cas de surdosage en scopolamine, des effets indesirables peuvent se presenter sous forme de confusion mentale, d’agitation, d’irritabilite, d’hallucinations et de delires. Les auteurs rapportent un cas de surdosage de scopolamine, impliquant l’utilisation de 3 patchs Scopoderm®, chez un individu percute par un train a grande vitesse. Selon les informations communiquees par les enqueteurs, la victime aurait ete apercue par le conducteur du TGV circulant a 130 km/h, sautant du bord du quai a hauteur d’une gare de village. L’analyse du sang a montre une concentration en scopolamine a 5,2 ng/mL, ainsi qu’un usage therapeutique d’oxazepam et de clozapine. La concentration en scopolamine apparait comme largement superieure aux concentrations therapeutiques usuelles (

Summary A 21-year old male was arrested after killing a rival during a dramatic episode of violence, due to jealousy. The perpetrator was sent to prison, where he revealed, several months later, that he was using anabolic steroids at the time of the assault. The steroids were used to enhance his muscular mass. To document possible steroids abuse, a hair specimen (9 cm in length, black in colour) was collected 7 months after the event and segmented in 3 × 3 cm segments. A specific steroids screening procedure, involving both LC-MS/MS and GC-MS/MS, was used, which demonstrated the presence of drostanolone and its ester form, drostanolone enantate in the distal segment (i.e. the one corresponding to the period of the assault). Concentrations were 3 and 14 pg/mg for drostanolone and drostanolone enantate, respectively. The etiology of this murder was finally considered to be due to an aggressive behaviour, which can have been enhanced by side effects due to anabolic steroids abuse.

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 (3 525 ng/mL) and urine (7 384 ng/mL). The femoral blood concentration was higher than the fatal concentrations range already reported in the literature (from 50 to 3 200 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 (

A 59-year-old male was found dead at home, with two empty vials of an oily preparation obtained from a manufacturer from East Europe. There was no label on the vial. The subject was a former weightlifter, also known as an anabolic steroids abuser. The local prosecutor ordered a body examination, which was unremarkable, and allowed collecting femoral blood, urine and scalp hair (6 cm, brown). He was treated for cardiac insufficiency with quinidine. Biological specimens were submitted not only to standard toxicological analyses including a screening with liquid chromatography (LC)–quadrupole time of flight, but also to a specific LC–tandem mass spectrometry method for anabolic steroids testing. Ethanol was not found in both blood and urine. Quinidine blood concentration (791 ng/mL) was therapeutic. No drug of abuse was identified. In blood, testosterone was less that 1 ng/mL and no other steroid was identified. In urine, testosterone/epitestosterone was 1.56 and boldenone was present at a concentration of 9 ng/mL. The hair test results, performed on the whole length, demonstrated repetitive steroids abuse, including not only testosterone (140 pg/mg), testosterone propionate (605 pg/mg) and testosterone decanoate (249 pg/mg), but also boldenone (160 pg/mg), trenbolone (143 pg/mg) and metandienone (60 pg/mg). Since forensic laboratories have limited access to steroid urinary metabolite reference material due to specific regulations (to avoid testing athletes before anti-doping verifications), hair analyses seem to be the best approach to document anabolic agents abuse. Indeed, in hair, the target drug is the parent compound; in addition, when compared to blood or urine, this matrix has a much larger window of detection. The pathologist concluded cardiac insufficiency in a context involving repetitive abuse of anabolic drugs. This case indicates that more attention should be paid to anabolic steroids, in a context of sudden cardiac death.

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.

For 40 years, hair tests have been presented as the best approach to document long-term consumption of a drug. This unique property has found numerous applications in clinical, forensic, and occupational toxicology. However, since the beginning of its implementation in biology, external contamination, with an associated risk of false positive result, has been presented as the key in the final interpretation. Evidence of environmental contamination and subsequent health issues can be the task of any toxicologist. Because of recent progress of analytical equipment, it is now possible to quantify drugs in hair with high level of accuracy and specificity at the pg/mg range. Therefore, segmental hair tests can be used to document environmental contamination and are the objective of this publication. In a family law case, N,N-dimethyltryptamine (DMT), a powerful hallucinogen, has been found in the hair of the partner of a repetitive DMT smoker at 4 to 13 pg/mg in 6 × 1 cm segments, with a regular increase of concentrations from the proximal to the distal hair end. The low measured concentrations and the particular pattern of DMT distribution along the hair shaft seem to be typical of environmental contamination, the older hair (those of the distal part) being for a longer time in contact with the drug. Despite strong decontamination, drugs from the environment can remain bound to the hair matrix and therefore be able to be used to document environmental contamination.

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 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.

Resume L’usage de cathinones est un phenomene recent lie a l’emergence de nouvelles substances psychoactives. Certains groupes de la population peuvent etre davantage exposes comme, par exemple, les hommes qui ont des activites sexuelles avec d’autres hommes sous l’influence de substances psychoactives. Cette pratique porte le nom de « chemsex ». Les auteurs rapportent une observation originale qui a conduit au deces de facon indirecte d’un consommateur. Le matin a 10h30, une dispute eclate au sein d’un couple homosexuel. L’un d’eux pourrait etre consommateur de stupefiants. Il aurait consomme des cathinones plusieurs fois en deux jours. Afin d’eviter une phase de descente desagreable, il voulait consommer a nouveau des drogues, mais son conjoint s’y est oppose. A 20h35, l’individu est decouvert pendu sur son lieu de travail. A l’autopsie, les observations sont compatibles avec un mecanisme de pendaison. Une expertise toxicologique de reference est ordonnee, qui a mis en evidence de la 3-methylmethcathinone (3-MMC) dans les prelevements, selon les concentrations suivantes : sang femoral (49 ng/mL), sang cardiaque (53 ng/mL), urines (310 ng/mL), contenu gastrique (74 ng/mL) et bile (205 ng/mL). Une analyse en GC-MS a ete indispensable afin de differencier la 3-MMC et la 4-MMC (mephedrone). L’analyse des poils pubiens a donne les resultats suivants : 12 pg/mg de MDMA, 4 pg/mg de 3-MMC et 28 pg/mg de buphedrone. L’analyse d’une fiole retrouvee au domicile de la victime a mis en evidence de la buphedrone. Enfin, sur les vetements que portait la victime (tee-shirt et sous-vetement), il a ete retrouve de la 3-MMC ainsi que des traces de MDMA, de MDA et de buphedrone, demontrant un usage correspondant a la periode ou ils ont ete portes. Toutes les concentrations de 3-MMC sont probablement sous-estimees, du fait de l’instabilite chimique bien connue de cette molecule. Le suicide semble correspondre au phenomene de descente difficile, apres consommation repetee de stimulants. Les circonstances apparaissent comme superposables aux rares cas decrits dans la litterature, avec une prevalence importante de la pendaison.

Resume L’objectif de cet article est de presenter deux approches, l’une basee sur les analyses biochimiques et l’autre sur le dosage des oligo-elements dans les cheveux, afin d’explorer le statut nutritionnel d’enfants pour lesquels une denutrition est suspectee a l’autopsie. Nous presentons le cas d’une fillette de 9 mois decedee au domicile. Le corps est transporte a l’unite de mort inattendue du nourrisson le jour meme (j0) ou sont effectues differents prelevements. Des ecchymoses ayant ete constatees a l’examen du corps, un signalement est effectue et le corps transporte a l’institut medicolegal. L’autopsie effectuee a J1 revele un traumatisme crânien, cause du deces, et un retard staturoponderal majeur. Le magistrat ordonne, en plus de l’expertise toxicologique de reference, une evaluation du statut nutritionnel de l’enfant. Les analyses toxicologiques et biochimiques sont effectuees a partir des echantillons de serum preleve a J0 ainsi que de sang peripherique et de cheveux preleves a J1. Les analyses toxicologiques ne revelent aucune anomalie. Les parametres biochimiques doses dans le serum (albumine, pre-albumine, uree, creatinine, acide urique) et le sang total (β-hydroxybutyrate) sont normaux a l’exception d’une elevation de l’acide urique. Le dosage des oligo-elements dans les cheveux par ICP-MS montre des resultats comparables a ceux obtenus dans une population de sujets temoins et d’enfants de la meme tranche d’âge. L’examen anatomopathologique ne releve aucune lesion en faveur d’une denutrition. En conclusion, ces deux approches ont permis d’eliminer une denutrition. Bien que peu exploitee, l’approche par criblage des oligo-elements pourrait s’averer utile, notamment pour augmenter la fenetre de detection ou lorsque les prelevements necessaires aux analyses biochimiques ne sont pas disponibles. D’autres etudes de cas sont necessaires pour etayer cette hypothese.

During a party in another country, several adults sniffed a powder presented as being lysergic acid diethylamide (LSD). The next morning, two subjects, including a French citizen, were found dead. After a body examination that concluded that the death was due to respiratory and cardiac collapses, the French citizen’s corpse was returned to France and buried. Four years later, the body was exhumed, and an autopsy that did not reveal traumatic injury was performed. During the autopsy, biological specimens were collected. A comprehensive toxicological screening, followed by confirmation using ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS-MS) revealed the presence of 2,5-dimethoxy-4-chloamphetamine (DOC) in all specimens: liver (99 ng/g), spleen (28 ng/g), bone (14 ng/g), lung (15 ng/g) and pubic hair (32 pg/mg). No other drug, including pharmaceuticals and drugs of abuse were identified, but the circumstances of specimen collection can influence drug stability. Literature survey about DOC stability in biological material did not contribute in interpretation as there is no data dealing with storage for about 4 years before quantitative analysis. A stability study was performed at the laboratory. Blank blood was spiked with DOC at 1 mg/L, stored at + 4°C and −20°C and regularly tested over 6 months. The percentages of concentration remaining from the initial concentration of DOC stored for 6 months at + 4°C and −20°C were 53% and 59%, respectively. To characterize the metabolite(s) of DOC, the drug was incubated with a pool of human hepatic microsomes and the cofactors required to ensure the functioning of the main phase I enzymes. The incubation media were analyzed by liquid chromatography (LC) coupled to high-resolution mass spectrometry (MS), and the results showed hydroxy-DOC. However, the hydroxy-metabolite was not identified in the liver or spleen of the subject. Although the French pathologist considered that it was more likely than not a toxic death, it is difficult to attribute the death to DOC alone, as it was impossible to test for ethanol and other chemically instable drugs. This case presents original data, which can be useful to increase the knowledge in designer drug toxicity.

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.

Although it has been accepted by most scientists that drugs circulating in blood are eligible to hair incorporation, this cannot be considered as a general statement. A 42-year old man was found dead in his swimming pool. He was living alone, and seen alive 2 days before by a neighbour. Femoral blood, cardiac blood and hair were collected during body examination. Free morphine was identified in femoral blood at 28 ng/mL, corresponding to his treatment for chronic pain (3 × 5 mg daily for 4 months). However, with a limit of quantitation (LOQ) at 10 pg/mg, segmental hair testing (3 × 1 cm) for morphine was negative. In this paper, the author has reviewed the different factors which can be responsible of this discrepancy. Several variables can influence the detection of a drug in hair and the author has listed reasons that can account for the absence of analytical response in hair after drug administration. The drug may not be incorporated in hair. That is the case for large bio-molecules, such as hormones, which cannot be transferred from the blood capillaries to growing cells of hair. Cosmetic treatments (perming, colouring, bleaching) or environmental aggressions (ultraviolet radiation, thermal application) will always reduce the concentrations. In this case, the lack of morphine detection was attributed to the effects of chlorinated water from the swimming pool. A negative hair result is also a result. However, this can be interpreted in three different ways: 1. the owner of the hair did not take or was not exposed to the specific drug, 2. the procedure is not sensitive enough to detect the drug, or 3. something happened after drug incorporation (cosmetic treatment, environmental influence).

Resume Les auteurs rapportent le cas d’une patiente de 29 ans traitee par rilpivirine pour une infection au VIH et presentant un syndrome de cushing iatrogene peu de temps apres l’instauration du budesonide. Devant l’hypothese d’une possible accumulation de budesonide dans l’organisme, les auteurs ont mis en avant une interaction entre un glucocorticoide de synthese et un inhibiteur non nucleosidique de la transcriptase inverse (NNRTI), le budesonide et la rilpivirine. Cette evaluation a ete realisee in vitro par des microsomes hepatiques humains. Les medicaments ont ete administres a des doses therapeutiques. Les cliniciens ont suppose que le syndrome de cushing iatrogene pouvait etre la consequence d’une accumulation de budesonide dans l’organisme. Dans un premier temps, afin de caracteriser sur le plan chromatographique (temps de retention, transitions) les deux metabolites principaux du budesonide (16α-OH-prednisolone et 6s-OH-budesonide), un volontaire sain a consomme 2,2 mg de budesonide, et ses urines sont prelevees durant 24 h. Une methode originale par UHPLC/MS-MS a ainsi ete mise en place. Dans un second temps, la possible interaction entre la rilpivirine et le budesonide est evaluee avec comme support des microsomes hepatiques humains (HLMs). Il est observe, lors de l’incubation simultanee, une diminution de la production des deux metabolites du budesonide et d’une accumulation de la molecule mere. Avec une concentration en rilpivirine a 10 mg/L, il est observe une augmentation de la reponse en budesonide de 41,4 % alors que celle des metabolites diminue, de 69,0 % pour le 16α-OH-prednisolone et de 59,2 % pour le 6s-OH-budesonide. Il a ete conclu que la rilpivirine est un inhibiteur probable du cytochrome CYP3A4, et agit ainsi sur la metabolisation du budesonide. Cette observation apparait comme la premiere etude existante permettant de prouver l’interaction in vitro entre ces deux molecules.