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Francoise Bressolle - One of the best experts on this subject based on the ideXlab platform.
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Ibogaine and norIbogaine structural analysis and stability studies use of lc ms to determine alkaloid contents of the root bark of Tabernanthe Iboga
Journal of Liquid Chromatography & Related Technologies, 2007Co-Authors: V Kontrimaviciūtė, O Mathieu, L Balas, R Escale, Jean Pierre Blayac, Francoise BressolleAbstract:Abstract The aim of this study was: i) to carry out a structural analysis of Ibogaine and norIbogaine, ii) to identify products formed under light exposure (daylight or 254 nm, 20°C) of the two drugs in methanolic solutions, and iii) to examine the alkaloid contents of a specimen of root bark of the Tabernanthe Iboga shrub using liquid chromatography‐electrospray mass spectrometry. After daylight exposure, two oxidation products were detected: ibochine and iboluteine from Ibogaine, and desmethoxyibochine and desmethoxyiboluteine from norIbogaine. After exposure to 254 nm of the Ibogaine solution, another compound that could possibly be the analogous lactam of iboluteine was detected. From the liquid chromatography electrospray‐mass spectrometry analysis of the root barks of a specimen of the Tabernanthe Iboga shrub, seven alkaloids were detected: ibochine (m/z 325), Ibogaline (m/z 341), iboluteine (m/z 327), Ibogaine (m/z 311), Ibogamine (m/z 281) and voacangine (m/z 369). The last compound characterized ...
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liquid chromatography electrospray mass spectrometry determination of Ibogaine and norIbogaine in human plasma and whole blood application to a poisoning involving Tabernanthe Iboga root
Journal of Chromatography B, 2006Co-Authors: Violeta Kontrimaviciute, O Mathieu, Jeanclaude Mathieudaude, Helene Breton, Francoise BressolleAbstract:Abstract A liquid chromatography/electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the first time for the determination of Ibogaine and norIbogaine in human plasma and whole blood. The method involved solid phase extraction of the compounds and the internal standard (fluorescein) from the two matrices using Oasis ® HLB columns. LC separation was performed on a Zorbax eclipse XD8 C8 column (5 μm) with a mobile phase of acetonitrile containing 0.02% (v/v) trimethylamine and 2 mM ammonium formate buffer. MS data were acquired in single ion monitoring mode at m / z 311.2, 297.2 and 332.5 for Ibogaine, norIbogaine and fluorescein, respectively. The drug/internal standard peak area ratios were linked via a quadratic relationship to plasma (0.89–179 μg/l for Ibogaine; 1–200 μg/l for norIbogaine) and to whole blood concentrations (1.78–358 μg/kg for Ibogaine; 2–400 μg/kg for norIbogaine). Precision ranged from 4.5 to 13% and accuracy was 89–102%. Dilution of the samples had no influence on the performance of the method. Extraction recoveries were ≥94% in plasma and ≥57% in whole blood. The lower limits of quantitation were 0.89 μg/l for Ibogaine and 1 μg/l for norIbogaine in plasma, and 1.78 μg/kg for Ibogaine and 2 μg/kg for norIbogaine in whole blood. In frozen plasma samples, the two drugs were stable for at least 1 year. In blood, Ibogaine and norIbogaine were stable for 4 h at 4 °C and 20 °C and 2 months at −20 °C. The method was successfully used for the analysis of a poisoning involving Tabernanthe Iboga root.
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distribution of Ibogaine and norIbogaine in a man following a poisoning involving root bark of the Tabernanthe Iboga shrub
Journal of Analytical Toxicology, 2006Co-Authors: V Kontrimaviciūtė, O Mathieu, Jeanclaude Mathieudaude, Paulius Vainauskas, Thierry Casper, Eric Baccino, Francoise BressolleAbstract:In the present paper, we report for the first time the tissue distribution of Ibogaine and norIbogaine, the main metabolite of Ibogaine, in a 48-year-old Caucasian male, with a history of drug abuse, found dead at his home after a poisoning involving the ingestion of root bark from the shrub Tabernanthe Iboga. Ibogaine and norIbogaine were quantified in tissues and fluids using a fully validated liquid chromatography-electrospray mass spectrometry method. Apart from cardiac tissue, Ibogaine and norIbogaine were identified in all matrices investigated. The highest concentrations were found in spleen, liver, brain, and lung. The tissue/subclavian blood concentration ratios averaged 1.78, 3.75, 1.16, and 4.64 for Ibogaine and 0.83, 2.43, 0.90, and 2.69 for norIbogaine for spleen, liver, brain, and lung, respectively. Very low concentrations of the two drugs were found in the prostatic tissue. Both Ibogaine and norIbogaine are secreted in the bile and cross the blood-brain harrier. Four other compounds were detected in most of the studied matrices. One of them was identified as Ibogamine. Unfortunately, we were not able to positively identify the other three compounds because of the unavailability of reference substances. Two of them could possibly be attributed to the following oxidation products: iboluteine and desmethoxyiboluteine. The third compound could be Ibogaline.
Ricardo Reyes-chilpa - One of the best experts on this subject based on the ideXlab platform.
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Strategies for the in vitro production of antiaddictive Ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture (PCTOC), 2019Co-Authors: Felix Krengel, Josefina Herrera-santoyo, Teresa De Jesús Olivera-flores, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the Ibogan type, such as Ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international Ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe Iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative Ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive Ibogan type MIAs coronaridine, Ibogamine, voacangine, and Ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other Ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type. This review aims at giving an overview of potential strategies to produce antiaddictive Ibogan type alkaloids from in vitro cultures of Apocynaceae species.
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Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)
Chemistry & Biodiversity, 2019Co-Authors: Felix Krengel, Marco V. Mijangos, Marisol Reyes-lezama, Ricardo Reyes-chilpaAbstract:: Several species from the Apocynaceae family, such as Tabernanthe Iboga, Voacanga africana, and many Tabernaemontana species, produce Ibogan type alkaloids, some of which present antiaddictive properties. In this study, we used gas chromatography/mass spectrometry (GC/MS) to examine the efficiency of methanol, acetone, ethyl acetate, dichloromethane, chloroform, and hydrochloric acid in extracting the antiaddictive compounds coronaridine, Ibogamine, voacangine, and Ibogaine (altogether the CIVI-complex) from the root barks of Tabernaemontana alba and Tabernaemontana arborea. These Mexican species have recently shown great potential as alternative natural sources of the aforementioned substances. Methanol proved to be the most suitable solvent. Furthermore, the crude methanolic extracts could be engaged in a one-step demethoxycarbonylation process that converted coronaridine and voacangine directly into its non-carboxylic counterparts Ibogamine and Ibogaine, respectively, without the intermediacy of their carboxylic acids. The established protocol straightforwardly simplifies the alkaloid mixture from four to two majority compounds. In summary, our findings facilitate and improve both the qualitative and quantitative analysis of CIVI-complex-containing plant material, as well as outlining a viable method for the bulk production of these scientifically and pharmaceutically important substances from Mexican Tabernaemontana species.
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Strategies for the in vitro production of antiaddictive Ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture, 2019Co-Authors: Felix Krengel, Teresa De Jesús Olivera-flores, Josefina Herrera-santoyo, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the Ibogan type, such as Ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international Ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe Iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative Ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive Ibogan type MIAs coronaridine, Ibogamine, voacangine, and Ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other Ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type.
Felix Krengel - One of the best experts on this subject based on the ideXlab platform.
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Strategies for the in vitro production of antiaddictive Ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture (PCTOC), 2019Co-Authors: Felix Krengel, Josefina Herrera-santoyo, Teresa De Jesús Olivera-flores, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the Ibogan type, such as Ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international Ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe Iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative Ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive Ibogan type MIAs coronaridine, Ibogamine, voacangine, and Ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other Ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type. This review aims at giving an overview of potential strategies to produce antiaddictive Ibogan type alkaloids from in vitro cultures of Apocynaceae species.
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Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)
Chemistry & Biodiversity, 2019Co-Authors: Felix Krengel, Marco V. Mijangos, Marisol Reyes-lezama, Ricardo Reyes-chilpaAbstract:: Several species from the Apocynaceae family, such as Tabernanthe Iboga, Voacanga africana, and many Tabernaemontana species, produce Ibogan type alkaloids, some of which present antiaddictive properties. In this study, we used gas chromatography/mass spectrometry (GC/MS) to examine the efficiency of methanol, acetone, ethyl acetate, dichloromethane, chloroform, and hydrochloric acid in extracting the antiaddictive compounds coronaridine, Ibogamine, voacangine, and Ibogaine (altogether the CIVI-complex) from the root barks of Tabernaemontana alba and Tabernaemontana arborea. These Mexican species have recently shown great potential as alternative natural sources of the aforementioned substances. Methanol proved to be the most suitable solvent. Furthermore, the crude methanolic extracts could be engaged in a one-step demethoxycarbonylation process that converted coronaridine and voacangine directly into its non-carboxylic counterparts Ibogamine and Ibogaine, respectively, without the intermediacy of their carboxylic acids. The established protocol straightforwardly simplifies the alkaloid mixture from four to two majority compounds. In summary, our findings facilitate and improve both the qualitative and quantitative analysis of CIVI-complex-containing plant material, as well as outlining a viable method for the bulk production of these scientifically and pharmaceutically important substances from Mexican Tabernaemontana species.
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Strategies for the in vitro production of antiaddictive Ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture, 2019Co-Authors: Felix Krengel, Teresa De Jesús Olivera-flores, Josefina Herrera-santoyo, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the Ibogan type, such as Ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international Ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe Iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative Ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive Ibogan type MIAs coronaridine, Ibogamine, voacangine, and Ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other Ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type.
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metabolite profiling of anti addictive alkaloids from four mexican tabernaemontana species and the entheogenic african shrub Tabernanthe Iboga apocynaceae
Chemistry & Biodiversity, 2019Co-Authors: Felix Krengel, Quentin Chevalier, Jonathan Dickinson, Josefina Herrera Santoyo, Ricardo Reyes ChilpaAbstract:: Ibogaine and other Ibogan type alkaloids present anti-addictive effects against several drugs of abuse and occur in different species of the Apocynaceae family. In this work, we used gas chromatography-mass spectrometry (GC/MS) and principal component analysis (PCA) in order to compare the alkaloid profiles of the root and stem barks of four Mexican Tabernaemontana species with the root bark of the entheogenic African shrub Tabernanthe Iboga. PCA demonstrated that separation between species could be attributed to quantitative differences of the major alkaloids, coronaridine, Ibogamine, voacangine, and Ibogaine. While T. Iboga mainly presented high concentrations of Ibogaine, Tabernaemontana samples either showed a predominance of voacangine and Ibogaine, or coronaridine and Ibogamine, respectively. The results illustrate the phytochemical proximity between both genera and confirm previous suggestions that Mexican Tabernaemontana species are viable sources of anti-addictive compounds.
O Mathieu - One of the best experts on this subject based on the ideXlab platform.
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Ibogaine and norIbogaine structural analysis and stability studies use of lc ms to determine alkaloid contents of the root bark of Tabernanthe Iboga
Journal of Liquid Chromatography & Related Technologies, 2007Co-Authors: V Kontrimaviciūtė, O Mathieu, L Balas, R Escale, Jean Pierre Blayac, Francoise BressolleAbstract:Abstract The aim of this study was: i) to carry out a structural analysis of Ibogaine and norIbogaine, ii) to identify products formed under light exposure (daylight or 254 nm, 20°C) of the two drugs in methanolic solutions, and iii) to examine the alkaloid contents of a specimen of root bark of the Tabernanthe Iboga shrub using liquid chromatography‐electrospray mass spectrometry. After daylight exposure, two oxidation products were detected: ibochine and iboluteine from Ibogaine, and desmethoxyibochine and desmethoxyiboluteine from norIbogaine. After exposure to 254 nm of the Ibogaine solution, another compound that could possibly be the analogous lactam of iboluteine was detected. From the liquid chromatography electrospray‐mass spectrometry analysis of the root barks of a specimen of the Tabernanthe Iboga shrub, seven alkaloids were detected: ibochine (m/z 325), Ibogaline (m/z 341), iboluteine (m/z 327), Ibogaine (m/z 311), Ibogamine (m/z 281) and voacangine (m/z 369). The last compound characterized ...
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liquid chromatography electrospray mass spectrometry determination of Ibogaine and norIbogaine in human plasma and whole blood application to a poisoning involving Tabernanthe Iboga root
Journal of Chromatography B, 2006Co-Authors: Violeta Kontrimaviciute, O Mathieu, Jeanclaude Mathieudaude, Helene Breton, Francoise BressolleAbstract:Abstract A liquid chromatography/electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the first time for the determination of Ibogaine and norIbogaine in human plasma and whole blood. The method involved solid phase extraction of the compounds and the internal standard (fluorescein) from the two matrices using Oasis ® HLB columns. LC separation was performed on a Zorbax eclipse XD8 C8 column (5 μm) with a mobile phase of acetonitrile containing 0.02% (v/v) trimethylamine and 2 mM ammonium formate buffer. MS data were acquired in single ion monitoring mode at m / z 311.2, 297.2 and 332.5 for Ibogaine, norIbogaine and fluorescein, respectively. The drug/internal standard peak area ratios were linked via a quadratic relationship to plasma (0.89–179 μg/l for Ibogaine; 1–200 μg/l for norIbogaine) and to whole blood concentrations (1.78–358 μg/kg for Ibogaine; 2–400 μg/kg for norIbogaine). Precision ranged from 4.5 to 13% and accuracy was 89–102%. Dilution of the samples had no influence on the performance of the method. Extraction recoveries were ≥94% in plasma and ≥57% in whole blood. The lower limits of quantitation were 0.89 μg/l for Ibogaine and 1 μg/l for norIbogaine in plasma, and 1.78 μg/kg for Ibogaine and 2 μg/kg for norIbogaine in whole blood. In frozen plasma samples, the two drugs were stable for at least 1 year. In blood, Ibogaine and norIbogaine were stable for 4 h at 4 °C and 20 °C and 2 months at −20 °C. The method was successfully used for the analysis of a poisoning involving Tabernanthe Iboga root.
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distribution of Ibogaine and norIbogaine in a man following a poisoning involving root bark of the Tabernanthe Iboga shrub
Journal of Analytical Toxicology, 2006Co-Authors: V Kontrimaviciūtė, O Mathieu, Jeanclaude Mathieudaude, Paulius Vainauskas, Thierry Casper, Eric Baccino, Francoise BressolleAbstract:In the present paper, we report for the first time the tissue distribution of Ibogaine and norIbogaine, the main metabolite of Ibogaine, in a 48-year-old Caucasian male, with a history of drug abuse, found dead at his home after a poisoning involving the ingestion of root bark from the shrub Tabernanthe Iboga. Ibogaine and norIbogaine were quantified in tissues and fluids using a fully validated liquid chromatography-electrospray mass spectrometry method. Apart from cardiac tissue, Ibogaine and norIbogaine were identified in all matrices investigated. The highest concentrations were found in spleen, liver, brain, and lung. The tissue/subclavian blood concentration ratios averaged 1.78, 3.75, 1.16, and 4.64 for Ibogaine and 0.83, 2.43, 0.90, and 2.69 for norIbogaine for spleen, liver, brain, and lung, respectively. Very low concentrations of the two drugs were found in the prostatic tissue. Both Ibogaine and norIbogaine are secreted in the bile and cross the blood-brain harrier. Four other compounds were detected in most of the studied matrices. One of them was identified as Ibogamine. Unfortunately, we were not able to positively identify the other three compounds because of the unavailability of reference substances. Two of them could possibly be attributed to the following oxidation products: iboluteine and desmethoxyiboluteine. The third compound could be Ibogaline.
Thomas Gicquel - One of the best experts on this subject based on the ideXlab platform.
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Comparative molecular networking analysis of a Rauwolfia plant powder and biological matrices in a fatal ingestion case
Forensic Toxicology, 2020Co-Authors: Sophie Allard, Isabelle Morel, Brendan Le Daré, Pierre-marie Allard, Thomas GicquelAbstract:Identifying xenobiotics involved in deaths remains a challenge in toxicology, especially when they are missing from the usual suspect databases. The tool development for the rapid processing of untargeted screening data is a valuable asset. In recent years, the molecular networking has been developed in various fields, including toxicology, because of its ability to graphically display and compare complex data acquired from tandem mass spectrometry. Here, we report a case of fatal poisoning by ingestion of an unknown powder (labelled as Tabernanthe Iboga) and apply molecular networking to tentatively identify the plant involved in a woman’s death. The supposedly ingested powder, an authentic Tabernanthe Iboga root powder and postmortemed biological samples (peripheral blood and bile) were extracted and analyzed according to a screening method using high resolution liquid chromatography hyphenated to tandem mass spectrometry (Q-Exactive®). Analysis of these four matrices by molecular networking revealed a cluster of nodes composed of indolomonoterpenic alkaloids, a characteristic of the Apocynaceae family (Ibogaine, Ibogamine, ajmaline, reserpiline, yohimbine). Analysis of the spectral annotations of the supposedly ingested powder also shows a majority of occurrences related to the genus Rauwolfia, which differed from the authentic Tabernanthe Iboga root powder. Molecular networking allowed us to discard the Tabernanthe Iboga identification hypothesis and suggest an alternate Apocynaceae species, most likely belonging to the Rauwolfia genus. In addition, eleven putative compounds could be detected by the molecular networking, many of which seemed to be metabolites of the major components in the Rauwolfia genus.
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Comparative molecular networking analysis of a Rauwolfia plant powder and biological matrices in a fatal ingestion case
Forensic Toxicology, 2020Co-Authors: Sophie Allard, Isabelle Morel, Brendan Le Daré, Pierre-marie Allard, Thomas GicquelAbstract:Purpose Identifying xenobiotics involved in deaths remains a challenge in toxicology, especially when they are missing from the usual suspect databases. The tool development for the rapid processing of untargeted screening data is a valuable asset. In recent years, the molecular networking has been developed in various fields, including toxicology, because of its ability to graphically display and compare complex data acquired from tandem mass spectrometry. Here, we report a case of fatal poisoning by ingestion of an unknown powder (labelled as Tabernanthe Iboga ) and apply molecular networking to tentatively identify the plant involved in a woman’s death. Methods The supposedly ingested powder, an authentic Tabernanthe Iboga root powder and postmortemed biological samples (peripheral blood and bile) were extracted and analyzed according to a screening method using high resolution liquid chromatography hyphenated to tandem mass spectrometry (Q-Exactive^®). Results Analysis of these four matrices by molecular networking revealed a cluster of nodes composed of indolomonoterpenic alkaloids, a characteristic of the Apocynaceae family (Ibogaine, Ibogamine, ajmaline, reserpiline, yohimbine). Analysis of the spectral annotations of the supposedly ingested powder also shows a majority of occurrences related to the genus Rauwolfia , which differed from the authentic Tabernanthe Iboga root powder. Conclusions Molecular networking allowed us to discard the Tabernanthe Iboga identification hypothesis and suggest an alternate Apocynaceae species, most likely belonging to the Rauwolfia genus. In addition, eleven putative compounds could be detected by the molecular networking, many of which seemed to be metabolites of the major components in the Rauwolfia genus.
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reseaux moleculaires en toxicologie medico legale application a une suspicion d intoxication a Tabernanthe Iboga
Toxicologie Analytique et Clinique, 2018Co-Authors: Sophie Allard, Isabelle Morel, Pierre-marie Allard, Le F Devehat, Thomas GicquelAbstract:Objectif Nous appliquons a un cas d’intoxication fatale due a l’ingestion d’une poudre vendue comme Tabernanthe Iboga, une approche analytique utilisee dans le domaine de la chimie des substances naturelles: la generation de reseaux moleculaires. L’objectif est ici de determiner l’identite botanique de la plante en cause dans le deces de la patiente et d’explorer les relations structurales entre les metabolites retrouves dans les fluides biologiques et ceux presents dans la poudre vegetale. Methode La poudre de plante et les prelevements biologiques (sang peripherique et bile) ont ete extraits et analyses selon une methode de screening non ciblee par un couplage LC-MS/MS en haute resolution (Orbitrap, Q Exactive®, Thermo Scientific) sur une colonne Gold PFP (150 × 2,1 mm, 3 μm). Apres conversion, les donnees spectrales ont ete pre-traitees avec le logiciel MZmine2 puis chargees sur le serveur GNPS ( http://gnps.ucsd.edu ) afin de generer le reseau moleculaire correspondant. Celui-ci permet d’organiser les spectres de fragmentation acquis en fonction de leur similarite spectrale et donc de grouper les analytes en fonction de leur similarite structurale. Les nœuds dont les spectres de masses sont semblables seront ainsi regroupes au sein de clusters. L’annotation des donnees MS est faite au niveau MS1 via une base de donnees bibliographiques (Dictionnary of Natural Products) et au niveau MS2 via une base de donnee spectrale fragmentee in silico restreinte aux Apocynaceae et via les bases de donnees spectrales experimentales du serveur GNPS. Resultats 1) L’analyse visuelle du reseau moleculaire multi-matrices (sang, bile, poudre a identifier et poudre de racines de T. Iboga) revele l’existence d’un cluster constitue de nœuds issus a la fois des liquides biologiques et des extraits de plantes, indiquant la presence de molecules structurellement proches au sein des 4 echantillons 2) L’annotation des nœuds montre que ce cluster est principalement constitue d’alcaloides de type indolo-monoterpeniques caracteristiques de la famille des Apocynaceae. Plus specifiquement deux nœuds annotes comme Ibogaine et Ibogamine sont retrouves dans la poudre de T. Iboga mais sont absents des matrices biologiques et de la poudre non identifiee. Trois nœuds annotes comme ajmaline, reserpine et yohimbine sont eux partages entre les matrices bile, sang et poudre non identifiee. La presence de ces trois alcaloides suggere que la poudre ingeree provient d’une plante du genre Rauwolfia sp. 3) Cette information est corroboree par l’analyse des meta-donnees des annotations spectrales de la poudre non identifiee qui indique une majorite d’occurrences rattachee au genre Rauwolfia. 4) Par ailleurs l’observation du cluster montre plus de nœuds appartenant a la bile qu’au sang: ces molecules structurellement similaires sont de possibles metabolites des alcaloides du genre Rauwolfia. Conclusion L’approche par reseau moleculaire est parfaitement adaptee a l’analyse des donnees complexes obtenues lors de methodes de screening non ciblees acquises en HRMS. De maniere interessante, cet outil de visualisation des donnees spectrales permet l’obtention d’informations cles avant meme l’etape d’annotation. Enfin, l’utilisation de bases de donnees spectrales theoriques generees par fragmentation in silico, permet d’elargir les champs d’applications en toxicologie medico-legale notamment lorsque les composes recherches sont absents des bases de donnees classiques.
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death related to consumption of rauvolfia sp powder mislabeled as Tabernanthe Iboga
Forensic Science International, 2016Co-Authors: Thomas Gicquel, Chloe Hugbart, Francoise Lohezicle Devehat, Sylvie Lepage, Alain Baert, R Bouvet, Isabelle MorelAbstract:Powdered roots of Iboga (Tabernanthe Iboga) contain Ibogaine, an alkaloid that has been used to treat addictions. We report the case of a 30-year-old woman who died after ingesting a powder labeled as Tabernanthe Iboga she had bought online. Analysis of the powder revealed the absence of Ibogaine but the presence of toxic alkaloids (ajmaline, yohimbine and reserpine) found in Rauvolfia sp. plant species. An original and specific LC–MS/MS method developed to quantify ajmaline, yohimbine and reserpine showed respective concentrations of 109.1 ng/mL, 98.2 ng/mL and 30.8 ng/mL in blood, and 1528.2 ng/mL, 914.2 ng/mL and 561.2 ng/mL in bile. Moreover, systematic toxicological analyses of biological samples showed the presence of oxazepam at therapeutic concentration and cannabinoids. Death could be attributed to ingestion of a substantial quantity of crushed roots of Rauvolfia in association with concomitant drug withdrawal.
