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Clinical Analytics: Toxicological Screening/ Screening for Drugs of Abuse

Clinical Analytics: Toxicological Screening/ Screening for Drugs of Abuse. Martin Slusarczyk & Dino Wu 9th of Oct 2012. Quick overview. What are legal highs ? Mechanism of the action of neurotransmitters Overview of psychoactive substances and drug classes

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Clinical Analytics: Toxicological Screening/ Screening for Drugs of Abuse

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  1. Clinical Analytics: Toxicological Screening/ Screening for Drugs of Abuse Martin Slusarczyk & Dino Wu 9th of Oct 2012

  2. Quick overview • Whatare legal highs? • Mechanismoftheactionofneurotransmitters • Overviewofpsychoactivesubstancesanddrugclasses • Analytical strategyforourcase

  3. What are Legal Highs? • Psychoactive chemicals • In general: Possession and marketing are „legal“ (for the most part not anymore) • Origins: Synthetic or natural • Control problem, as little is known about these compounds.

  4. Steps of Neurotransmission

  5. General Effects of Legal Highs to the Neurotransmission • Similar structureto endogenous neurotransmitters • Agonist: Reductionofneurotransmitter reuptake • Antagonist: Interfering neurotransmitter synthesis or blocking of the postsynapticreceptors • Many possible consequences like: - Hallucinations- Paranoia- Euphoria- Panic Attacks- Anxiety

  6. Effect to Neurotransmission

  7. Mephedrone and Synthetic Cathinones

  8. Synthetic and Natural Tryptamines

  9. Synthetic Phenylethylamines

  10. Synthetic Phenylethylamines

  11. Cocaine Derivatives

  12. Ketamine and Phencyclidine Derivatives

  13. More Complex Structures

  14. „Legal High“ Situation in Switzerland • BetmKV art. 8 p. 1: Following narcotics cannot be cultivated, imported, produced or put into circulation: • - Opium or the remains after the production or consumation- Diacetylmorphine or its salts- Hallucinogens like lysergide (LSD-25)- Narcotics with Cannabis-like effects.

  15. „Legal High“ Situation in Switzerland • Since May 2011, a register for narcotics legal ordinance has been written with detailled informations about which compounds are controlled (like derivatives, salts)

  16. Considerationsfortheanalysis • Priorityisthehealthofthepatient -> Fast and quantitative

  17. What are we looking for? • The actualpsychoactivesubstances, drugs • Neglect extenders (Streckmittel), colourants.. • Askpatientwhether he tookdrugsandwhen. • Askformedicine he istaking (Perturbations?)

  18. Hair (onlyforlongtermanalysis) Sweat Nose -> cottonbuds (solid particles) Blood (dissolved) Sample ofchoice (due to high concentrations): Urine (dissolved) Whichsamples?

  19. Urine • Expected range: 10-1000 ng/ml (dependent on the compound) • Check of identity • One sample suffices, if additional blood samples are taken

  20. Quantification: Whichmethod ? • Atomicabsorption: forelements • Electrophoresis: CZE-DAD used, but lowsensitivity: enrichmentneeded • GC: volatile? Often derivatization neededGC-MS has the advantage to have a large reference library

  21. Confirmatorytest: LC-ESI-MS/MS • „Sensitive analysisofcompoundswith a widepolarityrange in samplesofvariousnature“ • Limits ofquantitation (LOQ): 1–100 ng/mL • Calibration: 10–10 000 ng/mL External calibration: Urine (healthy volunteer) Deuterated analogs (e.g. metabolites, opiates etc.) as internal standards -> recovery rate

  22. Sample preparation • Addition ofbuffers • Vortexing • LLE or SPE (Liquid liquid extraction or solid phase extraction) • Injection of 10 μl of the prepared urine into LC

  23. Blood - LC-ESI-MS/MS • Comparison to LC-EI-GC: • Fasterasnoderivatizationisneeded • Lessspecificfragmentsandfewerspectraofdatabanks • Normally expected range: 10-500 ng/ ml • Calibration: 1–1000 ng/mL (also lower conc.) Blood (healthyvolunteer) -> externalcalib. Deuterated analogs (e.g. metabolites, opiates etc.) asinternalstandards -> recovery rate

  24. Matrix interferants: • Proteins ( ~ 10 000 Da) • Antibodies (~ 100 000 Da) • Clottingfactors (~ 50 – 300 000 Da) • Wide range of lipophilic substances (disturb ionization process)

  25. Sample preparation • Addition ofbuffers • Add a dropofAcNto sample, thencentrifugation (cells, proteins) • Injectioninto LC

  26. Interpretation anderrorsources • Analysis by skilled professionals • Time passedsincedrugintake • Matrix interferences

  27. Thank You For Your Attention

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