Toxicological Screening – Legal Highs

Toxicological Screening – Legal Highs
Case
At 1:00 a.m. a 23 year old male patient is admitted to the emergency department
of the University Hospital in Basel. He was very agitated, had a combative violent
behavior and hallucination. He has been found in his home standing on his bed
complaining of mice everywhere. He was given the antidote for opiate
intoxications without any effect. The classical drugs of abuse screening tests in
the laboratory were negative. The physicians then suspected the intake of legal
highs or research chemicals and sent a urine and a blood sample to the
laboratory.
Questions
1. Which compounds are used as legal highs?
2. What is the action of these substances?
3. Which are the methods of choice for the analysis of these compounds?
4. How is the legal situation with these compounds in Switzerland?
Legal Highs
Synonyms: Designer Drugs ; Research Chemicals ; NPS (new psychoactive Substances)
=
Synthetic psychoactive Compounds, high similarity to common illegal Drugs, but
with structural modification to underpass drug restrictions
Sold as: bath salts, pond cleaner, air refresher, stain remover, plant food, insect
repellants, …
2009: more than 1300 products have been identified in England containing legal highs [1]
[1] Schmidt MM, Sharma A, Schifano F, Feinmann C (2011) „Legal highs“ on the net-Evaluation of UK-based-Websites, products and product information. Forensic Sci Int 206:92–97
Neurotransmitter
The psychoactive behavior of drugs is often based on the structural similarity to
endogenous neurotransmitters
γ-Aminobutyric acid,
GABA
Dopamine
Noradrenaline
Serotonin
Drug interaction with signaling of synapses
• Inhibition of the action potential
• Blocking of ion channels, altering electrical transmission
• Interference with synthesis of neurotransmitter
• Interference with storage, release, or uptake of neurotransmitter
• Interference with binding of neurotransmitter to a target cell receptor
• Interference with enzymatic breakdown of excess or unused transmitter
Synthetic and Natural Phenylethylamines
Dopamine
Methamphetamin,
Crystal Meth
Cathinon
Methedrone,
MCAT, Miaow Miaow
MDMA, Ecstasy
Methylone,
Explosion
Cathinon 
natural product from
Cath plant (catha edulis)
Synthetic and Natural Tryptamines
Serotonin
α-Methyltryptamine;
AMT
Psilocin
Bufotenin
N,N-diallyl-5-methoxytryptamine;
5-MeO-DALT
LSD
N,N-Dipropyltryptamine;
DPT
Magic mushroom
(Psilocybe semilanceata)
Cane toad (Rhinella marina)
Legal Situation in Switzerland
Problem: “Nulla poena sine lege certa“ (no penalty without definite law)
 Substances are ”easily” modified slightly and therefore legal
 In 2011 approx. 50 new substances added to list
The Analytical Challenge
Rapidly evolving market
 No data for Toxicokinetics and Toxicodynamics available
 No Standard material for control available
Drug analysis
 Circumstances
 Time
 Cost
 Method
 LC/MS
 GC/MS
 Immunoassay
 Sample
 Blood
 Urine
 Hair
Sample preparation
 Chain of custody
 Chronological documentation
 Paper trail
 Traceability
Sample
 Urine
 High concentrations
 Blood
 Serum / Plasma
 Shortterm analysis
 Complex preparation
 Hair
 Longterm analysis
 Nose
 Solid particles
GC
 Pro
 Specific retention times
 Easy to handle
 Autosampling
 Con
 Derivatisation
 Only volatiles
 Thermal stability
EI full-scan GC trace obtained from the analysis of a standard mixture of amphetamines.
HPLC
 Pro
 High troughput
 No derivatisation
 Autosampling
 Con
 Less specific
 More expensive than GC
MS detection




Specific fingerprints
Databases
Coupling with GC or HPLC
MS/MS for better determination
Structure and postulatet fragmentation pathway, EI full-scan mass spectrum
Immunoassays
 Pro
 Fast
 Specific binding of antibody (paratope) to antigen (epitope)
 Con
 No MS coupling
 No automation
 Single substance analysis
References
 www.scdat.ch; Swiss Guidelines Commitee for Drugs of Abuse Testing
 Wileyonlinelibrary.com

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