Alkaloïden zijn gifstoffen die vrijkomen wanneer de plant wordt blootgesteld aan omgevingsstress. Stikstof is een karakteristiek element, aanwezig in de chemische structuur van alkaloïden. Aangezien stikstof een van de belangrijkste brandstoffen voor de plant is, spelen alkaloïden een prominente rol in het overlevingsmechanisme. Voor de mens zijn alkaloïden echter schadelijk en kunnen ze chronische ziekten uitlokken zoals kanker. Contaminatie tijdens de thee oogst, zorgt ervoor dat deze gifstoffen in de wereldhandel terecht komen. Er is nood aan meer toegankelijke en efficiënte screeningstechnieken, zodat gecontamineerde thee tijdig kan opgespoord worden. Deze nieuwe methoden zullen op termijn de markt en volksgezondheid beter beschermen.
Thee, na water de meest geconsumeerde drank ter wereld. Toch komen de mogelijke gezondheidsrisico’s de laatste jaren steeds meer aan het licht. Het European Food Safety Authority (EFSA) concludeerde in augustus 2016, dat thee veruit de belangrijkste bijdrage levert aan de menselijke alkaloïde blootstelling. Alkaloïden vormen een verscheiden groep, die kan onderverdeeld worden in verschillende klassen met elk hun specifieke eigenschappen. In deze scriptie werd specifiek gefocust op Pyrrolizidine-alkaloïden (PA). De meest voorkomende contaminatieroute is gerelateerd aan het tegelijkertijd oogsten van verschillende gewassen, die dezelfde cyclus delen. Hierdoor kunnen de thee bladeren in contact komen met giftige alkaloïde-producerende planten.
Toxiciteit
De Pyrrolizidine-alkaloïden zijn gevaarlijk aangezien ze de celkern kunnen binnendringen en zo het DNA beschadigen. Dit proces vindt voornamelijk plaats in de lever, daarom zijn hepatocyten het belangrijkste doelwit van toxiciteit. De gemiddelde blootstelling aan PA, overschrijdt vaak de door de autoriteiten voorgestelde maximale inname. Blootstelling is in de meeste gevallen onvoldoende om vergiftiging te veroorzaken, maar kan een uitlokkende factor zijn voor chronische ziekten zoals leverkanker.
Screening resultaten
Een eerste doelstelling van deze scriptie, was een ruw idee te krijgen over de PA-contaminatie in commercieel beschikbare thee. De screening gebeurde met een reeds ontwikkelde methode, beschikbaar in het laboratorium. 15 verschillende theestalen werden geanalyseerd. Natuurlijk was het lage aantal gescreende monsters niet representatief voor de hele markt. Toch was het aantal gecontamineerde stalen opvallend hoog. In 14 van de 15 geanalyseerde monsters werd een PA-contaminatie vastgesteld. De gedetecteerde PA-types in de verschillende theesoorten kwamen exact overeen met de verwachtingen gebaseerd op literatuur onderzoek. De resultaten gaven dus een eerste indicatie dat de wereldwijde bezorgdheid rond dit onderwerp terecht is en de objectieven van deze scriptie waardevol zijn.
CCS databanken als extra identificatie zekerheid
Ion mobility spectrometry (IMS) is uitgegroeid tot een krachtige scheidingstechniek waarbij de gegenereerde ionen worden gescheiden op basis van hun mobiliteit. De mobiliteit (drifttijd) van een ion hangt af van zijn lading, grootte en vorm. De drifttijden zijn instrument- en toepassing specifiek, daarom is de parameter niet praktisch in gebruik. Om instrumentvergelijking mogelijk te maken, kan gebruik gemaakt worden van collision cross-section parameter (CCS). Deze techniek is relatief nieuw in het gebied van voedselveiligheid, vanwege het ontbreken van CCS databanken. Dankzij deze databanken zouden toxines via hun drifttijd geïdentificeerd kunnen worden, wat zorgt voor een extra identificatie zekerheid. In deze scriptie werd de eerste CCS-databank -voor 35 door de EU gereguleerde PA- aangemaakt.
De databank werd gecreëerd met behulp van twee wiskundige algoritmen (AllCCS en CCSbase), getraind door machine learning. CCS biedt de mogelijkheid om het identificatieproces verder te verbeteren, gebaseerd op unieke fysico-chemische eigenschappen van een molecule. In tegenstelling tot conventionele massaspectrometrie met behulp van m/z-verhoudingen, worden componenten gescheiden op basis van hun specifieke chemische structuur. Een CCS-database voor PA werd nooit eerder gerapporteerd. Na het vergelijken van experimentele CCS waarden en de theoretische CCS voorspellingen, bevestigden de lage prediction errors het voordeel van de aangemaakte CCS databank voor PA.
Methodetransfer naar gebruiksvriendelijke routine techniek
Momenteel worden PA in thee meestal gescreend met behulp van een Time Of Flight (TOF) analyser. Gezien de hoge complexiteit en kost, zijn deze analysers onhaalbaar in de industrie en enkel beschikbaar in gespecialiseerde laboratoria. Er is behoefte om de TOF-screeningmethode om te zetten naar een meer gebruiksvriendelijke en minder dure Triple quadrupole (QqQ)-methode. In deze scriptie werd de eerste verkenning van een nieuw en snel QqQ protocol beschreven voor de gelijktijdige bepaling van 21 PA in theemonsters. Na optimalisatie en validatie van de ontwikkelde methode, kan deze in de toekomst toegepast worden in de industrie. Zo zal men commerciële thee op een efficiënte en routinematige manier kunnen screenen en kan vermeden worden dat gecontamineerde thee de markt bereikt.
Waardevolle technieken voor de toekomst
De wereldwijde bezorgdheid en interesse rond dit onderwerp wordt gerechtvaardigd door de toenemende meldingen van PA-contaminatie. Op vlak van wereldhandel en voedselveiligheid zouden zowel toegankelijke, routinematige kwantificering als meer geavanceerde screeningtechnieken met behulp van CCS-databases meer aandacht moeten krijgen. Op deze manier kan voorkomen worden dat gecontamineerde thee op de markt komt en een ernstig risico vormt voor de volksgezondheid.
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