Thesis (Ph.D.) - University of Glasgow, 2007. / Ph.D. thesis submitted to the Department of Forensic Medicine and Science, University of Glasgow, 2007. Includes bibliographical references. Print version also available.

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Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [137]-146).

Les méthodes actuelles d’analyse pour rechercher des xénobiotiques et/ou leurs métabolites dans les liquides biologiques peuvent dans certaines occasions manquer de sensibilité. Ainsi, il est souvent difficile de mettre en évidence les substances utilisées par des agresseurs pour commettre des actes délictuels sur leurs victimes (vols ou encore viols), parce que ces substances administrées en très faibles quantités ont généralement des demi-vies courtes, ou que les recherches de ces substances se font plusieurs jours après l’agression. De même dans le cadre de l’exposition aux polluants de l’environnement et particulièrement aux hydrocarbures aromatiques polycycliques, il est difficile de mettre en évidence l’importance de l’exposition de salariés ou encore de la population générale à ces composés. Dans le cadre de la soumission chimique, l’utilisation de la chromatographie en phase liquide couplée à la spectrométrie de masse en tandem (MS / MS) permet d’obtenir une sensibilité suffisante notamment en mode MRM pour détecter des substances ou leurs métabolites dans les liquides biologiques de victimes. L’utilisation de la même technologie permet de rechercher les métabolites hydroxylés des hydrocarbures aromatiques polycycliques. Les objectifs du travail ont été de montrer l’applicabilité de la spectrométrie de masse dans deux domaines. Le premier se rapporte à la soumission chimique, domaine dans lequel après avoir rappelé, les définitions, la prévalence des cas de soumission chimique en Europe et dans les pays anglophones, la liste des substances psychoactives incriminées, les difficultés couramment rencontrées lors des investigations et les recommandations pour améliorer la détection des substances aux niveau des analyses toxicologiques, est rapporté un cas de soumission chimique par le diéthylamide de l'acide lysergique ou LSD, par mise en évidence de ce composé et de son métabolite principal par UPLC-MS/MS. Au cours du travail sur la mise en évidence des substances de la soumission chimique, nous avions préparé les extraits biologiques en mélangeant des extraits effectués à pH acide et alcalin et en ionisant les molécules en mode électrospray négatif et positif. Il est vite apparu que certaines molécules avaient une limite de détection trop élevée. Nous avons alors développé une méthode spécifique pour ces molécules afin d’améliorer leur détection. Le second domaine d’application a été la mise en évidence des métabolites hydroxylés des hydrocarbures aromatiques polycycliques. Dans un premiers temps, nous avons réalisé une revue générale de ces substances polluantes de l’environnement, puis nous avons validé par chromatographie liquide de haute performance couplée à la spectrométrie de masse une méthode qui permet d’identifier et de doser ces métabolites dans l’urine de sujets exposés ou non à ces HAP. / Les méthodes actuelles d’analyse pour rechercher des xénobiotiques et/ou leurs métabolites dans les liquides biologiques peuvent dans certaines occasions manquer de sensibilité. Ainsi, il est souvent difficile de mettre en évidence les substances utilisées par des agresseurs pour commettre des actes délictuels sur leurs victimes (vols ou encore viols), parce que ces substances administrées en très faibles quantités ont généralement des demi-vies courtes, ou que les recherches de ces substances se font plusieurs jours après l’agression. De même dans le cadre de l’exposition aux polluants de l’environnement et particulièrement aux hydrocarbures aromatiques polycycliques, il est difficile de mettre en évidence l’importance de l’exposition de salariés ou encore de la population générale à ces composés. Dans le cadre de la soumission chimique, l’utilisation de la chromatographie en phase liquide couplée à la spectrométrie de masse en tandem (MS / MS) permet d’obtenir une sensibilité suffisante notamment en mode MRM pour détecter des substances ou leurs métabolites dans les liquides biologiques de victimes. L’utilisation de la même technologie permet de rechercher les métabolites hydroxylés des hydrocarbures aromatiques polycycliques. Les objectifs du travail ont été de montrer l’applicabilité de la spectrométrie de masse dans deux domaines. Le premier se rapporte à la soumission chimique, domaine dans lequel après avoir rappelé, les définitions, la prévalence des cas de soumission chimique en Europe et dans les pays anglophones, la liste des substances psychoactives incriminées, les difficultés couramment rencontrées lors des investigations et les recommandations pour améliorer la détection des substances aux niveau des analyses toxicologiques, est rapporté un cas de soumission chimique par le diéthylamide de l'acide lysergique ou LSD, par mise en évidence de ce composé et de son métabolite principal par UPLC-MS/MS. Au cours du travail sur la mise en évidence des substances de la soumission chimique, nous avions préparé les extraits biologiques en mélangeant des extraits effectués à pH acide et alcalin et en ionisant les molécules en mode électrospray négatif et positif. Il est vite apparu que certaines molécules avaient une limite de détection trop élevée. Nous avons alors développé une méthode spécifique pour ces molécules afin d’améliorer leur détection. Le second domaine d’application a été la mise en évidence des métabolites hydroxylés des hydrocarbures aromatiques polycycliques. Dans un premiers temps, nous avons réalisé une revue générale de ces substances polluantes de l’environnement, puis nous avons validé par chromatographie liquide de haute performance couplée à la spectrométrie de masse une méthode qui permet d’identifier et de doser ces métabolites dans l’urine de sujets exposés ou non à ces HAP

"Synthetic Cannabinoids are among newly synthetized drugs that have become widely known throughout the United States and around the world. Originally, these compounds were used by researchers to isolate the medicinal effects of natural cannabis. Ultimately these compounds found their way into the illicit drug market as an alternative to marijuana. Unfortunately, the pharmacology of synthetic cannabinoids is not known in detail but it has been confirmed that they elicit stronger, more often times negative effects compared to natural cannabis. The use of these compounds have resulted in cases of overdose and even death. The National Forensic Laboratory Information System (NFLIS) collects drug report information involving narcotics, stimulants, depressants, hallucinogens, cannabis, and emerging drugs such as anabolic steroids, phenethylamines, and synthetic cannabinoids, to name a few. They receive drug reports from forensic laboratories and perform statistical analysis to establish the prevalence of these drugs through out the United States. Specifically, the use of published NFLIS data sets from 2009-2013 and unpublished data set from 2013-2014 provided prevalence information from laboratories that have received synthetic cannabinoids in their forensic casework. The use of additional surveys and databases to supplement NFLIS data sets were used to better understand which particular groups of people are most likely to consume synthetic cannabinoids and in what specific regions. Understanding how common the abuse of synthetic cannabinoids provides information on how best to control them and potentially prevent health risks associated with their use. The prevalence of synthetic cannabinoid use has demonstrated an increasing-decreasing-increasing pattern throughout the years. The specific synthetic cannabinoids that have been identified in drug cases have changed over time to bypass the drug control laws. The future prevalence of these drugs is uncertain but knowledge of current patterns may help us to understand the state of this issue and plan for the future cases our forensic drug chemistry laboratories will face."

For thesis abstract select View Thesis Title, Contents and Abstract

For thesis abstract select View Thesis Title, Contents and Abstract

Pesticide poisoning is a global health concern with approximately three million cases being reported on an annual basis. The latter includes both intentional and unintentional poisonings. Organophosphorus and carbamate insecticides are frequently found to be ‘responsible’ for pesticide poisoning in developing countries. In South Africa, aldicarb is the most potent carbamate pesticide and is sold in the informal markets as Temik. It is colloquially known as “Two step” or “Galephirimi” resulting in numerous cases of acute poisoning, especially in urban areas. Underreporting of suspected or confirmed pesticide poisoning cases has been a problem encountered in the national notification systems. Although a number of carbamate poisonings have been identified at the Pretoria Medico-Legal Laboratory, the presence of carbamates in post-mortem samples is rarely confirmed analytically. This may be ascribed to insufficient sample preparation, analytical methods not being sensitive enough or storage conditions not being optimal or too long before analysis takes place. It is well documented that most analytical errors occur during the pre-analytical phase, leading to a high prevalence of inconclusive results being attained. This may possibly be due to pre-analytical degradation, binding to biological matrix or the analytical method not been sensitive enough for detection in collected samples. Post-mortem redistribution factors such as physicochemical properties of the xenobiotic compounds (pH, volume of distribution, protein binding affinity, bacterial biotransformation and lipophilicity), characteristics of the matrix, specimen collection procedure and the use of preservatives may also influence the carbamate stability. The primary aim of the study was to optimise the sample preparation and analysis of biological matrices for select carbamates using LC-MS/MS method. Additionally, to analyse pesticide samples sold by street vendors as well as post-mortem samples collected from suspected cases of carbamate intoxication to determine whether the developed method can detect carbamates in real samples. Assessment of the aldicarb decay kinetics was done by spiking biological samples (whole blood, plasma, urine) collected from consenting healthy volunteers. Post-mortem samples (blood, urine, stomach content) of suspected carbamate poisoning cases, were screened for possible carbamate compounds and their metabolites or breakdown products. Optimisation and validation of the method was performed using a high-performance liquid chromatography (HPLC) system coupled to a triple quadrupole mass spectrometer following different extraction methods. The system was operated in positive electrospray ionisation (ESI+) mode. Different columns, mobile phase buffers and cartridges were used to compare the chromatographic separation of the carbamate compounds. Validation according to ICH guidelines was done for aldicarb. A set of matrix-matched standard calibration curves, was constructed using Analyst (version 1.5.2) software. Initial sample preparation of carbamate pesticides using three different SPE cartridges proved to be unreproducible with poor recoveries of specific compounds due to the wide range of carbamate pesticide polarities, so this was abandoned for the stability testing and forensic samples tested. About 85% reduction of the concentration of aldicarb was seen in whole blood only at ambient temperature but was stable at lower temperatures. Stability proved to be better in plasma compared to whole blood, for aldicarb and its oxidation products. Aldicarb was stable in urine stored with boric acid preservative. The ideal storage temperature for biological samples containing these carbamate compounds was found to be -80°C. During analysis of forensic samples, unknown peaks were consistently detected which are believed to correspond to adulterants and diluents which are added to “backstreet” pesticides. A possible match of an organophosphate, terbufos, found in some “backstreet” pesticide products was detected in some of the post-mortem samples. Considering their different physicochemical properties and that several factors can influence the biodegradation of carbamate compounds, no extrapolation of results from one carbamate compound to another can be formulated. The development and validation of an analytical method to quantify aldicarb and its oxidation products (aldicarb sulfoxide and sulfone) in whole blood, plasma and urine, using the protein precipitation method and LC-MS/MS was successful. Method validation to quantify ten standard carbamate pesticides using SPE and UPLC-q-TOF/MS was unsuccessful. The LC-MS/MS technique was found to be a suitable tool for the quantitation of aldicarb and its oxidation products in typical post-mortem sample matrices. / Dissertation (MSc (Medical Criminalistics))--University of Pretoria, 2021. / Faculty of Health Sciences Research Committee / Department of Pharmacology / University of Pretoria Masters research and research award grant / Forensic Medicine / MSc (Medical Criminalistics) / Unrestricted

A análise de fluidos biológicos para detecção de usuários de Cannabis não é rotina em nossos serviços de toxicologia forense pela falta de um método aplicável às condições de trabalho desses laboratórios. Neste trabalho foi estudado um método que utiliza a cromatografia de camada delgada de alta eficiência (CCDAE) como técnica de identificação. Cinco mililitros de urina são submetidos à hidrólise alcalina e à extração Iíquido/líquido, com posterior aplicação do resíduo obtido na cromatoplaca. O limite de detecção em estudo realizado com adicionados foi de 5ng/ml. Urina de usuários de Cannabis quando submetidas a esta metodologia apresentaram resultado semelhante ao do padrão de THCCOOH, principal produto de biotransformação do THC. As amostras utilizadas como branco de referência não apresentaram mancha semelhante. Na análise das amostras de usuários por imunoensaio de fluorescência polarizada (\"cutoff\' 50ng/ml) obteve-se resultado negativo para usuários moderados e ocasionais. Com auxilio de curva-padrão observou-se que a concentração provável de canabinóides nessas amostras estaria entre 20-50ng/ml. No estudo comparativo dos resultados obtidos nas duas técnicas, foi verificada uma correspondência de 100% para as amostras de usuários com padrão de uso intenso. Nos usuários moderados e ocasionais não foi observada boa correspondência entre os resultados. / Abstract not available.

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