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  1. Article ; Online: Body fluid contamination in the context of an adverse analytical finding in doping: About a case involving ostarine.

    Alvarez, Jean-Claude / Etting, Isabelle / Larabi, Islam Amine

    Clinica chimica acta; international journal of clinical chemistry

    2024  Volume 557, Page(s) 117871

    Abstract: Ostarine, also known as MK-2866 or enobosarm, is a selective androgen receptor modulator (SARM). It has anabolic properties and as such is widely used in doping, accounting in 2021 for 25 % of the adverse analytical findings (AAF) among the class S1.2 " ... ...

    Abstract Ostarine, also known as MK-2866 or enobosarm, is a selective androgen receptor modulator (SARM). It has anabolic properties and as such is widely used in doping, accounting in 2021 for 25 % of the adverse analytical findings (AAF) among the class S1.2 "Other anabolic agents" of products banned by the World Anti-Doping Agency, to which it belongs. But in some cases, it can be responsible for an AAF following contamination. We report the case of an athlete who contaminated herself by exchanging body fluids while kissing her boyfriend, who took 25 mg per day of MK-2866 for 9 days prior to the athlete's AAF (urinary concentration evaluated at 13 ng/mL) without her knowledge. Both subjects came to our lab for hair testing. The athlete's hair was black and slightly frizzy. Six segments of 2 cm then 7 × 3 cm (33 cm) were analysed and showed increasing concentrations, from 2 pg/mg on the first segment to 17.8 pg/mg on the last segment. The boyfriend's hair, light-brown, analyzed on 4 × 2 cm, also showed increasing values, from 65 to 143 pg/mg. These gradients of concentration in the hair's athlete and in her boyfriend were compatible with external contamination of the hair, confirmed by analysis of washing baths, pillowcases (150 pg on each), and the athlete's hairbrush (250 pg). Fingernails were also contaminated, with 21 pg/mg in the athlete and 1041 pg/mg in the boyfriend, with highly contaminated washing baths, and toenails were less contaminated, with 2 pg/mg in the athlete and 17.3 pg/mg in the boyfriend. Urine samples taken 35 days after the start of MK-2866 treatment showed a value of 3690 ng/mL in the boyfriend and 5.7 ng/mL in the athlete. After 6 days off, these concentrations were 3.3 ng/mL and 0.1 ng/mL, respectively. A controlled transfer study was carried out 12 days after discontinuation (urine concentrations returned to negative level). After administration of 17 mg (the 25 mg/mL vial having been controlled at 17 mg/mL), urine samples were taken from the boyfriend and the athlete (n = 10 for each) for more than 25 h after they had been living normally with each other (regular kissing in particular). The boyfriend's urine concentrations ranged from 681 ng/mL to 12822 ng/mL (Tmax = 8:30 hrs), and the athlete's from 0.3 ng/mL to 13 ng/mL with Tmax = 8:30 hrs, i.e. at 22:30 hrs, which corresponded exactly to the time of collection of the urine that showed AAF, with a similar concentration. The dose ingested by the athlete was estimated at 15 µg. These results demonstrate the transfer of ostarine via body fluids between two subjects, with a high risk of AAF in one athlete, as observed in our case.
    MeSH term(s) Female ; Humans ; Anabolic Agents/urine ; Anilides ; Body Fluids/chemistry ; Doping in Sports ; Substance Abuse Detection/methods ; Male
    Chemical Substances Anabolic Agents ; Anilides ; ostarine (O3571H3R8N)
    Language English
    Publishing date 2024-03-11
    Publishing country Netherlands
    Document type Case Reports ; Journal Article
    ZDB-ID 80228-1
    ISSN 1873-3492 ; 0009-8981
    ISSN (online) 1873-3492
    ISSN 0009-8981
    DOI 10.1016/j.cca.2024.117871
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  2. Article ; Online: Evaluation of the cardiovascular risk induced by cannabis use from a series of 43 autopsy cases.

    Paul, Cotier / Charlotte, Mayer / Isabelle, Etting / de la Grandmaison Geoffroy, Lorin / Jean-Claude, Alvarez

    International journal of legal medicine

    2023  Volume 137, Issue 6, Page(s) 1725–1733

    Abstract: The aim of this monocentric observational autopsy study was to confirm the existence of a link between cannabis use and cardiovascular risk. It was based on the analysis of autopsy findings, cardiovascular pathological findings, and toxicological data in ...

    Abstract The aim of this monocentric observational autopsy study was to confirm the existence of a link between cannabis use and cardiovascular risk. It was based on the analysis of autopsy findings, cardiovascular pathological findings, and toxicological data in 43 autopsy cases of people who died with tetrahydrocannabinol (THC) in their blood over a 2-year period. Hair analysis was performed when available (n = 40) to distinguish between occasional and chronic cannabis use and to take into account other possible exposures, including smoking, drug consumption, and the use of other drugs of abuse (mainly cocaine, heroin, and amphetamine). A statistically significant association (Fisher's exact test, p < 0.001) was found between cannabis use, an undetermined manner of death, and the presence of an arrhythmogenic cardiac condition. An association was also found between cannabis use and the presence of advanced coronary heart disease (p = 0.01), heart disease (including ischemic heart disease, p = 0.003), or cardiomyopathy (p = 0.01). Through its systemic vascular action, cannabis could be a factor in triggering sudden death in subjects with arrhythmogenic cardiac conditions. In view of this finding, the mode of death of subjects who died in the presence of THC in the blood would in most cases be an "accident." These results highlight the potential adverse cardiac effects associated with cannabis use.
    Language English
    Publishing date 2023-08-31
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1055109-8
    ISSN 1437-1596 ; 0937-9827
    ISSN (online) 1437-1596
    ISSN 0937-9827
    DOI 10.1007/s00414-023-03079-x
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  3. Article ; Online: Le cannabidiol (CBD) : aspects analytiques et toxicologiques.

    Alvarez, Jean-Claude / Pelissier, Anne-Laure / Mura, Patrick / Goullé, Jean-Pierre

    Therapie

    2023  Volume 78, Issue 6, Page(s) 639–645

    Abstract: Cannabidiol (CBD) is a phytocannabinoid present in cannabis, obtained either by extraction from the plant or by synthesis. The latter has the advantage of being pure and contains few impurities, unlike CBD of plant origin. It is used by inhalation, ... ...

    Title translation Cannabidiol (CBD): Analytical and toxicological aspects.
    Abstract Cannabidiol (CBD) is a phytocannabinoid present in cannabis, obtained either by extraction from the plant or by synthesis. The latter has the advantage of being pure and contains few impurities, unlike CBD of plant origin. It is used by inhalation, ingestion or skin application. In France, the law stipulates that specialties containing CBD may contain up to 0.3% of tetrahydrocannabinol (THC), the psychoactive principle of cannabis. From an analytical point of view, it is therefore important to be able to quantify the two compounds as well as their metabolites in the various matrices that can be used clinically or forensically, in particular saliva and blood. The transformation of CBD into THC, which has long been suggested, appears to be an analytical artifact under certain conditions. CBD is not without toxicity, whether acute or chronic, as seems to attest to the serious adverse effects recorded by pharmacovigilance during the experiment currently being conducted in France by the Agence Nationale de Sécurité du Médicament et des Produits de Santé. Although CBD does not seem to modify driving abilities, driving a vehicle after consuming CBD containing up to 0.3% THC, and sometimes much more in products bought on the internet, can lead to a positive result in screening and confirmation tests by law enforcement agencies, whether salivary or blood tests, and therefore lead to a legal sanction.
    MeSH term(s) Humans ; Cannabidiol/adverse effects ; Dronabinol/adverse effects ; Drug-Related Side Effects and Adverse Reactions ; France
    Chemical Substances Cannabidiol (19GBJ60SN5) ; Dronabinol (7J8897W37S)
    Language French
    Publishing date 2023-02-20
    Publishing country France
    Document type English Abstract ; Journal Article
    ZDB-ID 603474-3
    ISSN 1958-5578 ; 0040-5957
    ISSN (online) 1958-5578
    ISSN 0040-5957
    DOI 10.1016/j.therap.2023.02.006
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  4. Article ; Online: Characterizing the risk related to the exposure to methylmercury over a lifetime: A global approach using population internal exposure.

    Gastellu, Thomas / Mondou, Anna / Bellouard, Marie / Alvarez, Jean-Claude / Le Bizec, Bruno / Rivière, Gilles

    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

    2024  Volume 187, Page(s) 114598

    Abstract: Seafood products accumulate methylmercury throughout the food chain and are the main source of methylmercury exposure. Methylmercury may trigger a number of adverse health effects, such as neurodevelopmental or nephrotoxic effects, the risk of which ... ...

    Abstract Seafood products accumulate methylmercury throughout the food chain and are the main source of methylmercury exposure. Methylmercury may trigger a number of adverse health effects, such as neurodevelopmental or nephrotoxic effects, the risk of which cannot be ruled out for the French high consumers of seafood. The characterisation of methylmercury-related risks is generally based on short-term dietary exposure without considering changes in consumption and exposure over the lifetime. Additionally, focusing on short-term dietary exposure, the fate of methylmercury (especially its accumulation) in the organism is not considered. The present study proposes a methodology basing risk characterization on estimates of body burden over a lifetime. First, trajectories of dietary exposures throughout lifetime were constructed based on the actual concentrations of total diet studies for a fictive representative French population, taking into account the social, economic and demographic parameters of individuals. Next, the fate of methylmercury in the body was estimated, based on these trajectories, using a specific physiologically-based kinetic (PBK) model that generated a representative pool of body burden trajectories. Simulated hair mercury concentrations were closed to previously reported French representative human biomonitoring data. Results showed that at certain stages of life, concentrations of methylmercury in hair were higher than the human biomonitoring guidance value set at 2.5 μg/g of hair by JECFA. This study showed the added value, in the case of substances accumulating in the body, of estimating dietary exposure over a lifetime and using exposure biomarkers estimated by a PBK model characterize the risk.
    MeSH term(s) Humans ; Methylmercury Compounds/toxicity ; Methylmercury Compounds/analysis ; Seafood/analysis ; Food Contamination/analysis ; Diet ; Dietary Exposure ; Mercury/analysis
    Chemical Substances Methylmercury Compounds ; Mercury (FXS1BY2PGL)
    Language English
    Publishing date 2024-03-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 782617-5
    ISSN 1873-6351 ; 0278-6915
    ISSN (online) 1873-6351
    ISSN 0278-6915
    DOI 10.1016/j.fct.2024.114598
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  5. Article: Characterization of 3-Hydroxyeticyclidine (3-HO-PCE) Metabolism in Human Liver Microsomes and Biological Samples Using High-Resolution Mass Spectrometry.

    Larabi, Islam Amine / Joseph, Delphine / Lesueur, Camille / Alvarez, Jean-Claude

    Metabolites

    2023  Volume 13, Issue 3

    Abstract: 3-Hydroxyeticyclidine (3-HO-PCE) is a ketamine derivative that produces dissociative, hallucinogenic, and euphoric effects when consumed, but little is known about its pharmacological properties, metabolism, and toxicity compared to other designer ... ...

    Abstract 3-Hydroxyeticyclidine (3-HO-PCE) is a ketamine derivative that produces dissociative, hallucinogenic, and euphoric effects when consumed, but little is known about its pharmacological properties, metabolism, and toxicity compared to other designer ketamine analogs. To address this gap in knowledge, this study explored for the first time the metabolism of 3-HO-PCE. Based on this investigation, it is hypothesized that combining the use of Human Liver Microsomes (HLM) as an In vitro model with urine and hair samples from drug users may enable the identification of key analytes that can extend the detection window of 3-HO-PCE, particularly in cases of overdose. The analysis identified 15 putative metabolites, 12 of which are produced through phase I metabolism involving
    Language English
    Publishing date 2023-03-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo13030432
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  6. Article ; Online: Consommer du CBD ou conduire, faut-il choisir ?

    Willeman, Théo / Micallef, Joëlle / Alvarez, Jean-Claude / Revol, Bruno

    Therapie

    2022  Volume 78, Issue 6, Page(s) 749–751

    Title translation Use CBD or drive, do you have to choose?
    Language French
    Publishing date 2022-12-05
    Publishing country France
    Document type Letter
    ZDB-ID 603474-3
    ISSN 1958-5578 ; 0040-5957
    ISSN (online) 1958-5578
    ISSN 0040-5957
    DOI 10.1016/j.therap.2022.11.006
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  7. Article ; Online: Metoclopramide Intoxication Through Breast Milk: Relevance of Blood and Hair Analyses.

    Bellouard, Marie / Abe, Emuri / Etting, Isabelle / Durrleman, Chloé / Alvarez, Jean-Claude

    Indian journal of pediatrics

    2023  Volume 90, Issue 3, Page(s) 314

    MeSH term(s) Female ; Humans ; Milk, Human ; Metoclopramide ; Lactation ; Hair
    Chemical Substances Metoclopramide (L4YEB44I46)
    Language English
    Publishing date 2023-01-25
    Publishing country India
    Document type Letter
    ZDB-ID 218231-2
    ISSN 0973-7693 ; 0019-5456
    ISSN (online) 0973-7693
    ISSN 0019-5456
    DOI 10.1007/s12098-022-04460-1
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  8. Article ; Online: Glyphosate and aminomethylphosphonic acid in human hair quantified by an LC-MS/MS method.

    Alvarez, Jean-Claude / Etting, Isabelle / Larabi, Islam Amine

    Biomedical chromatography : BMC

    2022  Volume 36, Issue 8, Page(s) e5391

    Abstract: An LC-MS/MS method for hair testing of glyphosate and aminomethylphosphonic acid (AMPA), its main biodegradation product, has been developed. After decontamination, 50 mg of hair was ground and sonicated in water for 2 h. The method was fully validated ... ...

    Abstract An LC-MS/MS method for hair testing of glyphosate and aminomethylphosphonic acid (AMPA), its main biodegradation product, has been developed. After decontamination, 50 mg of hair was ground and sonicated in water for 2 h. The method was fully validated in the 5-500 pg/mg range for glyphosate and 10-500 pg/mg for AMPA, and the limits of detection were 2 and 5 pg/mg, respectively. Matrix effect for glyphosate and AMPA was compensated by an isotope-labeled internal standard. Hair samples from four farmers who regularly used glyphosate and one farmer who used glyphosate but not his wife and 14 hair samples from nonoccupationally exposed subjects were tested. Glyphosate was found in head hair of three farmers, with concentration in the range 14-188 pg/mg. The fourth was found negative but with hair colored in red. Glyphosate was detected in 10 of 14 hair samples from nonoccupationally exposed subjects at concentrations of 11.5 pg/mg or lower and only in one segment (0-3 cm) of the farmer's spouse (6 pg/mg). AMPA was detected in five subjects, above the limit of quantification only in two of three occupationally exposed subjects with positive glyphosate. Further studies should be conducted to validate this potential new biomarker that could be useful for assessing long-term exposure to glyphosate.
    MeSH term(s) Chromatography, Liquid/methods ; Glycine/analogs & derivatives ; Hair/chemistry ; Herbicides/analysis ; Humans ; Organophosphonates ; Tandem Mass Spectrometry/methods ; Tetrazoles ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Glyphosate
    Chemical Substances Herbicides ; Organophosphonates ; Tetrazoles ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (77521-29-0) ; aminomethylphosphonic acid (AMPA) (90825O5C1U) ; Glycine (TE7660XO1C)
    Language English
    Publishing date 2022-05-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 632848-9
    ISSN 1099-0801 ; 0269-3879
    ISSN (online) 1099-0801
    ISSN 0269-3879
    DOI 10.1002/bmc.5391
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  9. Article ; Online: First detection/quantification of roxadustat in hair with a new liquid chromatography with tandem mass spectrometry method: Application to a treated patient.

    Alvarez, Jean-Claude / Etting, Isabelle / Juillard, Laurent / Massy, Ziad / Larabi, Islam-Amine

    Clinica chimica acta; international journal of clinical chemistry

    2023  Volume 546, Page(s) 117395

    Abstract: Roxadustat is an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase which increases erythropoiesis. It can therefore be used as a doping agent. No data are available on how to measure roxadustat in hair and on the concentration found in ... ...

    Abstract Roxadustat is an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase which increases erythropoiesis. It can therefore be used as a doping agent. No data are available on how to measure roxadustat in hair and on the concentration found in treated patients. The aim of this study was to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of roxadustat in hair and to apply it to a chronically treated patient. After decontamination with dichloromethane, testosterone-D3 used as an internal standard and phosphate buffer pH 5.0 were added to 20 mg of hair and incubated for 10 min at 95 °C. Four ml of dichloromethane were used for extraction and reconstituted into the mobile phase, 10 µL were injected into the chromatographic system. The method was linear in the range 0.5-200 pg/mg, accurate and precise (evaluated at 3 levels) and was successfully applied to measure roxadustat in a brown-haired patient treated pharmacologically with 100-120 mg 3 days a week. Results were stable between 41 and 57 pg/mg in the 6 proximal 1 cm segments. This first method describing the measurement of roxadustat in hair appears to be suitable for the quantification of this compound in clinical or doping control cases.
    MeSH term(s) Humans ; Tandem Mass Spectrometry/methods ; Chromatography, Liquid/methods ; Methylene Chloride/analysis ; Hair/chemistry
    Chemical Substances Methylene Chloride (588X2YUY0A)
    Language English
    Publishing date 2023-05-19
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80228-1
    ISSN 1873-3492 ; 0009-8981
    ISSN (online) 1873-3492
    ISSN 0009-8981
    DOI 10.1016/j.cca.2023.117395
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  10. Article ; Online: Hair and dietary supplements testing to identify contamination with roxadustat in an adverse analytical finding.

    Alvarez, Jean-Claude / Etting, Isabelle / Gheddar, Laurie / Kintz, Pascal / Larabi, Islam-Amine

    Journal of pharmaceutical and biomedical analysis

    2023  Volume 239, Page(s) 115915

    Abstract: Roxadustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase, which increases endogenous erythropoiesis. WADA has included roxadustat and other HIF stabilizers on its list of prohibited substances. We describe here the case of an ... ...

    Abstract Roxadustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase, which increases endogenous erythropoiesis. WADA has included roxadustat and other HIF stabilizers on its list of prohibited substances. We describe here the case of an elite athlete (female, 31 years old, 168 cm and 53 kg) with an adverse analytical finding (AAF) with concentration of roxadustat in her urine at 0.289 ng/mL in the A sample and 0.529 ng/mL in the B sample (83% higher than A). A stability study was carried out, showing total stability of roxadustat at this concentration in urine exposed to light for 50 h, so photoisomerization degradation cannot explain the difference in concentration. Her urine had been completely negative in a control test carried out three days previously, while roxadustat had been shown to be present in urine for at least 20 days after administration of pharmacologically effective doses to an athlete. Hair concentration was 0.39 and 0.35 pg/mg in the segments corresponding to the presumed period of intake, with few adjacent segments also positive (0.29-0.33 pg/mg), likely explained by cosmetic treatments. Concentrations found in a patient treated with a pharmacologically active dose (between 100 and 120 mg 3 days a week) were more than 100 times higher (between 41 and 57 pg/mg). Numerous supplements and pharmaceuticals taken by the athlete were analyzed. Only collagen powder showed the presence of roxadustat, at a very low but highly variable concentration (100 pg/g-1000 pg/g). A female volunteer (58 years old, 169 cm and 65 kg), taking this powder at the same doses as the athlete (10 g of powder 5 times for 6 days) presented 7 roxadustat-positive urine samples (although lower than those observed in the athlete) out of 34 sampled over 7 days, the difference in powder sampling location, age, weight, height, pharmacokinetic parameters variability and level of sporting activity between the athlete and the volunteer probably explaining the difference in concentrations observed. All these results could be consistent with an AAF due to contamination by dietary supplements, which are becoming increasingly common due to the current exposome of athletes in our society.
    MeSH term(s) Humans ; Female ; Adult ; Middle Aged ; Powders ; Glycine ; Isoquinolines/pharmacokinetics ; Dietary Supplements ; Renal Insufficiency, Chronic
    Chemical Substances Powders ; Glycine (TE7660XO1C) ; Isoquinolines
    Language English
    Publishing date 2023-12-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2023.115915
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