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GC/C/IRMS) Als Potentielle Untersuchungsmethode Zum Nachweis Einer Illegalen Anwendung Von 19-17 Βββ-Nortestosteron in Der Ebermast

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GC/C/IRMS) Als Potentielle Untersuchungsmethode Zum Nachweis Einer Illegalen Anwendung Von 19-17 Βββ-Nortestosteron in Der Ebermast Einsatz der Stabilisotopen-Massenspektrometrie (GC/C/IRMS) als potentielle Untersuchungsmethode zum Nachweis einer illegalen Anwendung von 19-17 βββ-Nortestosteron in der Ebermast Dissertation zur Erlangung des akademischen Doktorgrades der Naturwissenschaften an der Bergischen Universität im Fachbereich Mathematik und Naturwissenschaften Die Arbeit wurde in der Zeit vom 15. Mai 2003 bis 31.Dezember 2006 am Chemischen und Veterinäruntersuchungsamt in Freiburg angefertigt vorgelegt von Annette Mertineit-Heinz Wuppertal 2007 Diese Dissertation kann wie folgt zitiert werden: urn:nbn:de:hbz:468-20070870 [http://nbn-resolving.de/urn/resolver.pl?urn=urn%3Anbn%3Ade%3Ahbz%3A468-20070870] dem Allmächtigen Gott Das Geheimnis Gottes ist Jesus Christus, in dem alle Schätze der Weisheit und Erkenntnis verborgen sind. Die Bibel , Kolosser 2, 3 Dank Mein besonderer Dank gilt Herrn Prof. Dr. Michael Petz, der es mir ermöglichte, an der Universität Wuppertal diese Dissertation anzufertigen. Für seine Hilfsbereitschaft und Ermutigungen bin ich ihm sehr dankbar. Bedanken möchte ich mich beim Amtsleiter des CVUA Herrn Dr. Roland Renner sowie Laborleiter Herrn Dr. Martin Metschies, dass ich die Untersuchungen für diese Arbeit am CVUA durchführen durfte. Bei Laborleiterin Frau Dr. Eva Annweiler möchte ich mich für ihre vielseitige Unterstützung in analytischen Fragen und ihre Hilfe bei der Durchsicht der Arbeit bedanken. Den Labormitarbeitern Herrn Thomas Huber danke ich für die Unterstützung bei den EA/IRMS-Messungen, Frau Sylvia Scanlan-Sierra bei den GC/MS-Messung und Herrn Manfred Grosse bei den GC/FID-Messungen. Herr Grosse hat sich immer Zeit genommen, mich zu unterstützen, ohne dabei seine tägliche Arbeit zu vernach- lässigen. Für die Unterstützung der Aufarbeitung der Eberurine gilt mein Dank Laborleiter Herr Lippold und den Mitarbeitern Frau Annabarbara Fies, Herrn Markus Roth und Frau Maria Schmidt. Den Mitarbeitern aus Labor 34 danke ich für die Hilfe bei den ELISA-Messung sowie der Durchführung des Vorversuchs zur Festlegung der Untersuchungsmatrix. Ein großes Danke möchte ich Herrn Andreas Probst aussprechen. Ohne seine außergewöhnliche Hilfe, sein analytisches Wissen und seine Freundschaft wäre es vermutlich nicht zum Abschluss dieser Arbeit gekommen. Für die Eberproben und die Probenahme danke ich Frau Dr. Siegrid Polten sowie ihrem Team aus der Landesanstalt für Landwirtschaft und Gartenbau des Landes Sachen-Anhalt in Iden. Herrn Dr. Friedhelm Erschig danke ich für die Probennahme des Kastratenurins im Schlachthof Freiburg. Herrn Prof. Dr. Dr. Rolf Claus und Herrn Dr. Markus Lacorn an der Universität in Hohenheim danke ich für die Hilfe bei Fragen zu Steroiden. Auch bei Herrn Dr. Matthias Gehre vom Umweltforschungszentrum in Leipzig bedanke ich mich für die Hilfestellung bei gerätetechnischen Problemen. Mein größter Dank gilt meinen Eltern, die mir diese Ausbildung ermöglichten. Bedanken möchte ich mich auch bei meiner Tochter Anna-Maria, die während des Projektzeitraumes auf die Welt kam. Dank ihres zufriedenen Gemütes konnte ich die Arbeit ruhigen Gewissens beenden, was nicht zuletzt durch meine Schwiegereltern als tägliche Babysitter ermöglicht wurde. Allen voran bin ich meinem Mann für seine Unterstützung, Hilfe und Opferbereitschaft in allen Situationen, vor allem den schwierigen Momenten mehr als dankbar. Das Vertrauen auf den Herrn Jesus Christus gab mir die Kraft, trotz vieler teils unüberwindbarer Schwierigkeiten bis zum Ende durchzuhalten. Inhaltsverzeichnis Zusammenfassung................................................................................................................... 1 Abstract.................................................................................................................................... 3 Abkürzungen............................................................................................................................ 4 Theoretischer Teil..................................................................................................................... 6 1 Einleitung .......................................................................................................................... 6 2 Ebermast........................................................................................................................... 8 3 Chemie der Stabilisotopen .............................................................................................. 10 3.1 Begriffe..................................................................................................................... 10 3.2 Isotopendiskriminierung ........................................................................................... 12 3.3 Das Element Kohlenstoff und seine Diskriminierungsmöglichkeiten......................... 13 4 Eigenschaften der Steroide ............................................................................................. 17 4.1 Struktur und Nomenklatur der Steroide .................................................................... 17 4.2 Einteilung der Steroide............................................................................................. 21 4.3 Chemische und biochemische Eigenschaften der Steroide ...................................... 22 4.4 Wirkungs- und Regulationsmechanismus der Steroide ............................................ 23 4.5 Steroid-Biosynthese ................................................................................................. 23 13 12 4.6 Industrielle Partialsynthese und Einfluss auf das C/ C-Verhältnis der Steroide..... 27 4.7 Steroid-Metabolismus............................................................................................... 27 5 Androgene ...................................................................................................................... 30 5.1 Allgemeines ............................................................................................................. 30 5.2 Charakterisierung der anabolen Wirkung ................................................................. 31 5.3 Regulation und Wirkung der Androgene................................................................... 31 6 Nortestosteron................................................................................................................. 32 6.1 Allgemeine Eigenschaften........................................................................................ 32 6.2 Nortestosteron als anaboles Steroid......................................................................... 33 6.3 Nortestosteron als Arzneimittel................................................................................. 34 6.4 Illegale Anwendung.................................................................................................. 34 6.5 Biosynthese von Nortestosteron............................................................................... 35 6.6 Vorkommen von Nortestosteron............................................................................... 39 7 Analytik von Nortestosteron............................................................................................. 41 7.1 Quantitative Methoden ............................................................................................. 41 13 12 7.2 Bestimmung des C/ C-Verhältnisses.................................................................... 44 8 Messtechnik der GC/C/IRMS .......................................................................................... 45 8.1 Messprinzip.............................................................................................................. 45 8.2 Kalibrierung des CO 2-Referenzgases...................................................................... 47 8.3 Probenaufbereitung für die GC/C/IRMS Analytik ...................................................... 47 8.4 Derivatisierung für die GC/C/IRMS-Analytik ............................................................. 47 8.5 Verhalten der Substanzen auf der GC-Säule ........................................................... 49 9 Zielsetzung...................................................................................................................... 53 Ergebnisse und Diskussion .................................................................................................... 55 10 Einleitung und Überblick .............................................................................................. 55 11 Methodenentwicklung der Messmethoden................................................................... 55 11.1 Ermittlung und Optimierung der GC-Parameter........................................................ 55 11.2 GC/C/IRMS Parameter............................................................................................. 61 11.3 Einflüsse der Messtechnik auf den δ13 C-Wert........................................................... 65 12 Ermittlung des Probenmaterials und der Kontrollmaterialien........................................ 68 12.1 Probenmaterial......................................................................................................... 68 12.2 Festlegen des Precursors von Nortestosteron.......................................................... 69 12.3 Kontroll- oder Blankurin mit Standards ..................................................................... 70 13 Entwicklung der Aufarbeitungsmethode....................................................................... 72 13.1 Einleitung ................................................................................................................
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