Synthesis and Purification of Reference Materials for NPS
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Synthesis and Purification of Reference Materials for NPS Huiling Liu Chiron AS, Trondheim, Norway
Transcript of Synthesis and Purification of Reference Materials for NPS
Synthesis and Purification ofReference Materials for NPS
Huiling Liu
Chiron AS, Trondheim, Norway
• Environmental analysis
• Petroleum analysis
• Food safety analysis
• Pharmaceutical and forensic analysis
Chiron – Provider for reference materials
Reference materials for Pharmaceutical and Forensic analysis:
• Metabolites; Intermediates; Impurities
• Drugs of abuse:
• Opioids
• Cannabinoids
• Cocaines
• Amphetamines
• New Designer Drugs
Reference materials for NPSs:
• 2009: First to launch SPICE standards (JWH-018 and JWH-073)
• 2012-13: Standards for SPICE metabolites• 2010-13: Cathinones and Amphetamines• 2014- :
Reference materials for NPSs:
• 2009: First to launch SPICE standards (JWH-018 and JWH-073)
• 2012-13: Standards for SPICE metabolites• 2010-13: Cathinones and Amphetamines• 2014- :
new synthetic cannabinoids,designer benzodiazepines, GHB …
Projects for NPS reference materials:
• Industrial Ph.D (2012-2014)
- The Research Council of Norway
- Cooperated with NTNU
• ISOFOR (2012-2015)
- Innovation Norway
- Cooperated with NIPH
• Quantum SPICE (2013-2016)- EuroStars, European Funding
- Cooperated with Nal Van Minden
«QUANTUM SPICE»
• EUROSTARS -A collaborative research projectfor European SMEs
• Chiron AS, Norway• Nal von Minden GmbH , Germany
Nal von Minden GmbH:• Preparation of POCT (point of care tests) or
rapid tests for the same
Chiron AS:• Synthesis of CRMs for the identification and
quantification of «New PsychoactiveSubstances» by chromatography
SPICE (JWH) general structure:
N
R2
R1
O
SPICE general synthesis:
NH
Cl R1
O
NH
R1
O
N
R1
O
R2
+
R2-Cl
Spice metabolites
N
O
-OH
-OH
-OH
-CH2OH, -COOH
SPICE metabolite synthesis:
N
O
R1
N
R1
O
COOMe
Cl COOMe
N
R1
O
COOH
N
R1
O
CH2OH
LiAlH4
OH-
First Norwegian list (2012)AM-2201JWH-018JWH-073JWH-081JWH-122JWH-203JWH-210JWH-250
JWH-018 type (C5-alkyl)
N
O
N
O
JWH-018N
O
N
O
D
D
DD
DD
D
DDD
D
N
O
O
N
O
N
O
JWH-122
JWH-210
JWH-081
JWH-007
JWH-018 2-Methylnaphthoyl
JWH-122 d11
JWH-018 d11
N
F
O
N
F
O
AM-2201
MAM-2201
JWH-018 type metabolites
N
O
JWH-018
N
O
N
O
JWH-122
JWH-210
N
O
COOH
N
O
OH
N
O
F
AM-2201
+ d4 IS
N
O
OH
N
O
COOH
N
O
COOH
+ d4 IS
MAM-2201
cont. JWH-018 type metabolites
N
O
N
O
N
O
O
JWH-081
JWH-007
JWH-018 2-Methylnaphthoyl
N
O
OH
N
O
COOH
N
O
COOH
N
O
O
OH
+ d4 IS
+ d4 IS
RSC-4 metabolites
RSC-4
N
O
O
N
O O
N
O
O
RSC-4 ortho
RSC-4 meta
N
O
O
OH
N
O O
OH
N
O
O
OH
N
O
O
COOH
N
O O
COOH
N
O
O
COOH
+ d4 IS
+ d4 IS
+ d4 IS
JWH-073 type metabolites
N
O
N
O
N
O
O
N
O
JWH-073
JWH-016
JWH-073 2-Methylnaphthoyl
JWH-098
N
O
OH
N
O
COOH
N
O
OH
N
O
COOH
N
O
OH
N
O
COOH
N
O
O
OH
N
O
O
COOH
+ d4-IS
+ d4 IS
+ d4 IS
+ d4 IS
Phenylethanone type metabolites
N
O
Cl
N
O
O
JWH-203
JWH-250
N
O
O
RCS-8
N
O
Cl
OH
N
O
Cl
COOH
N
O
O
OH
N
O
O
COOH
+ d4 IS
+ d4 IS
Second Norwegian list (2013)
N
R
O
N
R
O
N
R
O
(F)
R=:
JWH type NSPs not covered by theNorwegian regulations 2013:
AB-001
Adamantyltype:
N
O
Amido-adamantyltype:
APICA
N
N
O
JWH type NSPs not covered by theNorwegian regulations 2013:
APINACA STS-135 (5F-APICA)
NN
N
O
NN
N
O
F
JWH type NSPs not covered by theNorwegian regulations 2013:
Cyclopropyltype:
N
N
O
N
O
F
AB-005 XLR-11
JWH type NSPs not covered by theNorwegian regulations 2013:
Carboxylic ester type:
N
O
O
N
QUPIC
Other compounds recently prepared:
AB-PINACA AB-FUBINACA
N
N
NH
O NH2
O
N
N
NH
O OH
O
N
N
NH
O OH
O
F
N
N
NH
O NH2
O
F
Other compounds recently prepared:
N
O
JWH-030
N
O
F
JWH-307
O
N N
O
URB754
Cathinones
NH2
O
NH
O
O
O
N
O
O
O
N
O
NH
O
NH
OF
NH
O
OH
NH
O
Cathinone
Ethylone
α-PVP
MDPV
Methylcathinone
2-FMC
4-Hydroxy-methcathinone
Mephedrone
Cathinones
NH2
O
NH
O
O
O
N
O
O
O
N
O
NH
O
NH
OF
NH
O
OH
NH
O
Cathinone
Ethylone
α-PVP
MDPV
Methylcathinone
2-FMC
4-Hydroxy-methcathinone
Mephedrone
NEW NPS-Compounds
25NBOMe-series, e.g. 25INOBMe
BTCP, BCP, Benoclidine
Methoxetamine, MXE
S
N
N
I
O
O
O
O
O NH
NN
F
NAdamantane
O
AKB-48, Apinaca
5F-AKB-48
NN
O
O
N
PB-22, QUPIC
5F-PB22
5MAPBO
NH
NN
F
O
O
N
NN
F
NAdamantane
O
Identity
• NMR• Mass spectrometry• UV-VIS spectrometry• Comparison with authentic
samples when available• Other (mp, IR etc.)
Purity
• Chemical purity by GC and/or LC• Solvent content by GC-MS analysis
(thermo deserption)• Water content by Karl-Fisher analysis• Inorganics by Ash content (sulphate ash)
«Chiron Gold Label CRMs»
• A Chiron 2013 project aiming to producehighest quality CRMs through
- ISO 17025 accreditation- ISO GUIDE 34 accreditation
• Will include the products from «ISOFOR» and «QUANTUM SPICE»
Challenges
• Many products:new products, unknown metabolites
• Large variations in chemical classes
• Small quantities
Future work on NSPs:
• Focus on important metabolites• 13C Labeling• New compounds
Ackowledgements:
Innovation NorwayEUROSTARS
The Norwegian Research Council
