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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
