Laboratoire LAT LUMTOX

Sainte-Foy-lès-Lyon, France

Laboratoire LAT LUMTOX

Sainte-Foy-lès-Lyon, France
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Carlier J.,Laboratoire LAT LUMTOX | Guitton J.,Laboratoire Of Toxicologie | Bevalot F.,Laboratoire LAT LUMTOX | Fanton L.,Institute medico legal | Gaillard Y.,Laboratoire LAT LUMTOX
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2014

The toxicity of the sea mango (Cerbera manghas L.) is well known. The plant is ranked as one of the deadliest of the southern Asian coastline. Cardenolidic heterosides are responsible for the cardiotoxicity of trees of the Cerbera genus. We have identified and determined the concentration of the principal glycosidic steroids present in the seeds of sea mangos (Thailand). Drug screening of an extract of the seeds was carried out using ultra-high performance liquid chromatography coupled to photodiode array detection and mass spectrometry (UHPLC-PDA-MS) with quantification at 219. nm. Identification was confirmed by UHPLC-HRMS. Deacetyltanghinin (m/. z 549.3055 ± 2. ppm), neriifolin (m/. z 535.3259 ± 2. ppm), tanghinin (m/. z 591.3169 ± 2. ppm) and cerberin (577.3375 ± 2. ppm) were the most abundant glycosidic steroids present in the sea mango seeds. A seed of the dried ripe fruit had concentrations of 1209.1, 804.2, 621.4 and 285.9. μg/g, respectively. A seed of the fresh unripe fruit had concentrations of 49.4, 47.0, 3.5 and 2.3. μg/g. © 2014 Elsevier B.V.


Cartiser N.,University Claude Bernard Lyon 1 | Cartiser N.,Laboratoire LAT LUMTOX | Bevalot F.,Laboratoire LAT LUMTOX | Bevalot F.,University Claude Bernard Lyon 1 | And 4 more authors.
International Journal of Legal Medicine | Year: 2011

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology. © 2010 Springer-Verlag.


Bevalot F.,Laboratoire LAT LUMTOX | Bevalot F.,University Claude Bernard Lyon 1 | Cartiser N.,University Claude Bernard Lyon 1 | Bottinelli C.,Laboratoire LAT LUMTOX | And 3 more authors.
Forensic Toxicology | Year: 2015

Forensic toxicology involves two possible levels of interpretation: qualitative (detection of xenobiotic consumption by the victim) and quantitative (assessing the implication of xenobiotics in death). Based on six drugs (meprobamate, morphine, cyamemazine, caffeine, diazepam, and citalopram) used as test substances, an animal experiment was combined with a series of autopsy cases to assess both qualitatively and quantitatively the use of bile and vitreous humor (VH) as alternative matrices to blood. The six molecules were administered to rabbits at various time points prior to euthanasia, and a human autopsy series (n > 20) was set up for each molecule. Bile, blood, and VH were analyzed using gas chromatography–tandem mass spectrometry (GC–MS/MS) according to two previously published methods. Ratios and correlations between bile/blood and VH/blood concentrations were determined. Both bile and VH demonstrated value qualitatively, allowing detection of all six molecules, possibly with longer detection windows than with blood. All six molecules showed a significant correlation between blood and VH concentrations in rabbits, whereas no such correlation was found in the autopsy series for cyamemazine or diazepam. In bile, correlations were found for meprobamate and caffeine in both rabbits and humans. Thus, bile and VH can be interpreted quantitatively for certain molecules. Combining the two experimental approaches demonstrated the impact of forensic (drug intake-to-death interval) and other parameters such as unbound fraction and molecular mass on xenobiotic distribution in these two alternative matrices. Pharmacokinetic and physicochemical parameters influencing the distribution of molecules were thus proposed, and were recommended to be taken into account when interpreting the behavior of other drugs. © 2014, Japanese Association of Forensic Toxicology and Springer Japan.


Bevalot F.,Laboratoire Lat Lumtox | Bevalot F.,University Claude Bernard Lyon 1 | Bottinelli C.,Laboratoire Lat Lumtox | Cartiser N.,University Claude Bernard Lyon 1 | And 3 more authors.
Journal of Analytical Toxicology | Year: 2014

An automated solid-phase extraction (SPE) protocol followed by gas chromatography coupled with tandem mass spectrometry was developed for quantification of caffeine, cyamemazine, meprobamate, morphine and 6-monoacetylmorphine (6-MAM) in 11 biological matrices [blood, urine, bile, vitreous humor, liver, kidney, lung and skeletal muscle, brain, adipose tissue and bone marrow (BM)]. The assay was validated for linearity, within-and between-day precision and accuracy, limits of quantification, selectivity, extraction recovery (ER), sample dilution and autosampler stability on BM. For the other matrices, partial validation was performed (limits of quantification, linearity, within-day precision, accuracy, selectivity and ER). The lower limits of quantification were 12.5 ng/mL(ng/g) for 6-MAM, morphine and cyamemazine, 100 ng/mL(ng/g) for meprobamate and 50 ng/ mL(ng/g) for caffeine. Analysis of real-case samples demonstrated the performance of the assay in forensic toxicology to investigate challenging cases in which, for example, blood is not available or in which analysis in alternative matrices could be relevant. The SPE protocol was also assessed as an extraction procedure that could target other relevant analytes of interest. The extraction procedure was applied to 12 molecules of forensic interest with various physicochemical properties (alimemazine, alprazolam, amitriptyline, citalopram, cocaine, diazepam, levomepromazine, nordazepam, tramadol, venlafaxine, pentobarbital and phenobarbital). All drugs were able to be detected at therapeutic concentrations in blood and in the alternate matrices. © The Author 2014. Published by Oxford University Press. All rights reserved.


Bevalot F.,Laboratoire LAT LUMTOX | Bevalot F.,University Claude Bernard Lyon 1 | Cartiser N.,University Claude Bernard Lyon 1 | Bottinelli C.,Laboratoire LAT LUMTOX | And 4 more authors.
Forensic Toxicology | Year: 2016

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015. © 2015, The Author(s).


PubMed | Laboratoire LAT LUMTOX and University Claude Bernard Lyon 1
Type: | Journal: Forensic toxicology | Year: 2016

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.


PubMed | Laboratoire LAT LUMTOX and University Claude Bernard Lyon 1
Type: | Journal: Forensic science international | Year: 2016

In forensic toxicology, alternative matrices to blood are useful in case of limited, unavailable or unusable blood sample, suspected postmortem redistribution or long drug intake-to-sampling interval. The present article provides an update on the state of knowledge for the use of bile in forensic toxicology, through a review of the Medline literature from 1970 to May 2015. Bile physiology and technical aspects of analysis (sampling, storage, sample preparation and analytical methods) are reported, to highlight specificities and consequences from an analytical and interpretative point of view. A table summarizes cause of death and quantification in bile and blood of 133 compounds from more than 200 case reports, providing a useful tool for forensic physicians and toxicologists involved in interpreting bile analysis. Qualitative and quantitative interpretation is discussed. As bile/blood concentration ratios are high for numerous molecules or metabolites, bile is a matrix of choice for screening when blood concentrations are low or non-detectable: e.g., cases of weak exposure or long intake-to-death interval. Quantitative applications have been little investigated, but small molecules with low bile/blood concentration ratios seem to be good candidates for quantitative bile-based interpretation. Further experimental data on the mechanism and properties of biliary extraction of xenobiotics of forensic interest are required to improve quantitative interpretation.


Mazoyer C.,Laboratoire LAT LUMTOX | Carlier J.,Laboratoire LAT LUMTOX | Boucher A.,Center Devaluation Et Dinformation Sur La Pharmacodependance Of Lyon | Peoc'h M.,Service de Medecine Legale | And 2 more authors.
Journal of Forensic Sciences | Year: 2013

We report the case of a man who died twelve hours after ingesting powdered iboga root, commonly taken for its stimulant and hallucinogenic properties. Ibogaine and ibogamine were quantified in the powder ingested and the victim's body fluids by GC-MS/MS after liquid-liquid extraction (Toxi-tubes A®). The concentrations of ibogaine measured in the blood samples taken at the scene and in the peripheral blood, urine, and gastric fluid samples taken during the autopsy were 0.65, 1.27, 1.7, and 53.5 μg/mL, while the iboga content in the powder was 7.2%. Moreover, systematic toxicological analyses of biological samples showed the presence of diazepam and methadone in therapeutic concentrations. Death was attributed to the ingestion of a substantial quantity of iboga in the context of simultaneous methadone and diazepam consumption. © 2013 American Academy of Forensic Sciences.


Imbert L.,Martin Luther University of Halle Wittenberg | Gaulier J.-M.,Martin Luther University of Halle Wittenberg | Dulaurent S.,Martin Luther University of Halle Wittenberg | Morichon J.,Martin Luther University of Halle Wittenberg | And 3 more authors.
International Journal of Legal Medicine | Year: 2014

Ethyl glucuronide (EtG) is a direct marker of ethanol consumption, and its assay in hair is an efficient tool for chronic alcoholism diagnosis. In 2012, the Society of Hair Testing proposed a new consensus for hair concentrations interpretation, strongly advising the use of analytical methods providing a limit of quantification of less than 3 pg/mg. The present work describes the optimization and validation of a previously developed liquid chromatography-tandem mass spectrometric method in order to comply with this recommendation. The concentration range of this improved method is from 3 to 1,000 pg/mg. Some cases are then described to illustrate the usefulness of hair EtG: a forensic post-mortem case and two cases of suspension of driving licences. Finally, hair samples of some teetotallers (n = 10) have been analyzed, which allowed neither to quantitate nor to detect any trace of EtG. © 2013 Springer-Verlag Berlin Heidelberg.


Priez-barallon C.,Laboratoire LAT LUMTOX | Carlier J.,Laboratoire LAT LUMTOX | Boyer B.,Institut Universitaire de France | Benslima M.,Institut Universitaire de France | And 3 more authors.
Journal of Analytical Toxicology | Year: 2014

Pregabalin is a drug for treating epilepsy, anxiety disorders and neuropathic pain. Cases of poisoning are rare, though some have been fatal. Concentrations of pregabalin in postmortem human samples and its distribution have very rarely been documented. As the literature is so scarce, we propose to report the concentrations in autopsy samples of 18 people who had been taking Lyrica®, including one case of a mixed overdose involving pregabalin. Analysis was carried out using an original Hydrophilic Interaction LIquid Chromatography (HILIC) technique coupled with a high-resolution mass spectrometer (m/z 160.1334 ± 5 ppm). The sensitivity of the technique enables a quick and simple treatment of the samples by protein precipitation. The method was validated in the whole blood with detection and quantification limits of 0.025 and 0.060 μg/mL, respectively. Pregabalin was a likely factor in the cause of death in 3 of the 18 cases. In the other individuals, the concentrations ranged from 0.4 to 17.0 in the peripheral blood, 1.5 to 11.1 in the central blood, 126.6 to 2004.6 in the urine and 10.5 to 58.3 μg/mL in the bile, with median values of 5.6, 4.6, 534.6 and 17.7, respectively. © The Author [2014]. Published by Oxford University Press. All rights reserved.

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