Analysis and Identification of
New Psychoactive Substances
What is NPS?
Novel chemical substances with psychoactive properties, designed on the basis of the chemical structure of a given parent drug and synthesized specifically for sale on the illicit market and to circumvent regulations on controlled substances.
Not controlled by the 1961 UN Single Convention on Narcotic Drugs or the 1971 UN Convention on Psychotropic Substances.
(fall under the wider class of substances called new psychoactive substances, NPS).
NPS
• These new psychoactive substances (NPS)
have been known in the market by terms such
as “designer drugs”, “legal highs”, “herbal highs”,
“bath salts”, “research chemicals”, “laboratory
reagents”.
What’s in NPS?
• Actually contain substances that are in fact
illegal and extremely harmful.
• Actually do not contain the advertised active
substances.
• Often contain chemicals that have never been
used in drugs for human consumption, and so
they haven’t been tested to show how safe or
unsafe they are.
• Give no indication of the psychoactive
substances in the list of ingredients.
New Psychoactive Substances,
NPS
These synthetic drugs fall into nine broad categories:
• Synthetic cannabinoids (known as spice or incense)
• Synthetic cathinones (known commercially as bath salts)
• Piperazines
• Plant-based substances
• Tryptamines
• Phenethylamines – 4-FA, PMMA
• Phencyclidine-type substances – Methoxetamine (MXE)
• Amininoidanes – 2-AI
• Other substances – Opioids, sedative
Synthetic Cannabinoids
What are synthetic cannabinoids?
Chemicals that mimic the actions or have a similar
structure to THC
• Classical – structurally related to THC
• Non-Classical – alternative structures, but
produces the same desired effects
Molecular Structures
Structures of Synthetic
Cannabinoids
N
O
CH3
N
O
CH3
CH3
N
O
CH3
N
O
CH3
CH3
N
O
CH3
CH3
??? JWH-018 JWH-073
JWH-018 2′ napthyl-N-(2-methylbutyl) isomer JWH-018-N-(2-methylbutyl)
isomer
JWH-018-N-(3-methylbutyl) isomer
Synthetic Cannabinoids Enchanced affinities (K1) for the cannabinoid
receptors.
Two pharamacologically distincit cannabinoid
receptors (CB1 and CB2) in human body (brains
and organs).
Synthetic canniobinoids –designated as
cannabidiods agonist that target the CB1
receptor.
Herbal products are sprayed with synthetic
cannabinoids.
When smoked, produce effects similar to those
of cannabis.
Baybean Blue Lotus
Siberian Motherwort Red Clover
Synthetic Cannabinoids
•JWH-018/073 arrived early and have come and gone.
•JWH-250 arrived a little later and as also cycled out.
•JWH-081 was part of a second wave that has already
completed its cycle.
•JWH-122 was part of the same wave but has persisted in
popularity.
•AM-2201 was part of the same second wave and has gained
in popularity.
•JWH-022 and JWH-210 are showing signs of increasing
popularity.
•In 2012 adamantoyl (AM-1248) and tetramethylcyclopropyl
(XLR-11 and UR-144) indoles which are ahead of the latest
attempts to schedule these drug classes.
Recently emergent substances are AMB-FUBINACA , MDMB-
CHMICA and 5-fluoro ADB
Synthetic Cannabinoids Trend
Synthetic Cathinones
What are synthetic cathinones?
• Related to parent compound, cathinone.
• Cathinone – monoamine alkaloid found in the
leaves of khat (catha edulis).
• Analogues of a corresponding phenethylamine.
• Sold in internet as ‘bath salts’.
NH2
O
Synthetic Cathinones
• Substitution at amine: Methcathinone or βk-
methamphetamine, ephedrone or N-
methylcathinone.
• Substitution of atom at benzyl ring: the most
prevalent of which appears to be mephedrone
(4-methylmethcathinone, 4-MMC ,3-FMC.
• Ring-substituted: methylone (βk-MDMA; 3,4-
methylenedioxy-N-methylcathinone), MDPV
(3,4-methylenedioxypyrovalerone), methedrone
(βk-PMMA; 4-methoxymethcathinone,) and PPP
(α-pyrrolidinopropiophenone).
Synthetic Cathinones
Synthetic Cathinones
• Produced by synthetic method.
• Precursor substances are readily available.
• Appear in various form – powder, tablet.
• Snorted, smoked, injected or taken orally.
• Psychoactive stimulant.
Synthetic Cathinones
Common Synthetic Cathinones
• Mephedrone*
• Methylone*
• MDPV*
• Ethylcathinones
• Methcathinones
• Fluorocathinones
• MXE
• MPPP
• 5-APB
• 6-APDB
• Butylone
• Naphyrone
• Pentedrone
• Pentylone
• Alpha-PVP
• Alpha-PBP
• Alpha-PVT
• 5-IAI
• MDAI
Ketamine
• Chemical name is 2-(2-chlorophenyl)-2-
(methylamino) cyclohexanone, an aryl cycloalkylamine.
• First synthesized in 1962 by Calvin Stevens at
Parke Davis laboratories in Michigan.
• Chiral centre of the cyclohexanone ring permits
the existence of two enantiomers
Ketamine
ClO
HN
Phenethylamines
• Refer to a class of substances with documented psychoactive and stimulant effects and include amphetamine, methamphetamine and MDMA, all of which are controlled under the 1971 Convention.
• The phenethylamines also include ring substituted substances such as the ‘2C series’, ring substituted amphetamines such as the ‘D series’ (e.g.DOI, DOC), benzodifurans (e.g. Bromo-Dragonfly, 2C-B-Fly) and others (e.g. p-methoxymethamphetamine (PMMA))
NH2
O
Br
O
2C-B
HN
CH3
CH3
OH3C
PMMA
Synthetic piperazines
• The best known piperazine that has been used as a
new psychoactive substance is 1-benzylpiperazine
(BZP)
• Other compounds such as 1-(3-chlorophenyl)
piperazine (mCPP), 1-(3-trifluoromethylphenyl)
piperazine (TFMPP) and, to a lesser extent, 1-
Benzyl-4-methylpiperazine (MBZP) and 1-(4-
Fluorophenyl) piperazine (pFPP) have been
identified on the market.
NH
NN
NH
CF3
1-Benzylpiperazine 1-(3-trifluoromethyl)phenylpiperazine
Plant-based substances
• Khat
• Kratom
• Salvia divinorum
• Catha edulis (of the celastraceae family)
• Consumed by chewing
• Contains number of chemicals.
• Active compounds : Cathione and cathine (pseudoephedrine).
• Leaves mature or dry, cathione is converted to cathine.
Khat
• Mitragyna speciosa Korth (of the Rubiaceae
family)
• Consumed fresh, although dried leaves in
powder form are also available
• Active compound : Mitragynine.
Kratom
• Salvia divinorum (of the mint family Lamiaceae)
• Consumed by sucking and chewing the fresh
leaves from a cigar-like roll or alternatively the
fresh leaves are crashed to make a drinkable
infusion
• Active compound : Salvinorin A.
Salvia divinorum
Miscellaneous substances
• Aminoindanes
• Phencyclidine-type substances
• Tryptamines
• Other substances – Opoids, sedative
What Are the Effects and Risks
of NPS?
The main effects of almost all ‘psychoactive’ drugs,
can be described using three main categories:
• Stimulants or ‘Uppers’
• ‘Downers’ or Sedatives
• Psychedelics or Hallucinogens
The use of NPS have been directly linked to
emergency hospital admissions and, in some
cases, deaths.
NPS in Malaysia
• First appearance in 2012
• Till now Dept of Chemistry had received
2 big cases of synthetic cannabinoids and synthetic cathinones
More than 100 small cases of tablets and powder contain synthetic cannabinoids, synthetic cathinones, synthetic piperazines and tryptamines
JWH-250
JWH-018
AM-2201
JWH-081
XLR-11
3-FMC
4-MMC
3,4-MDPV
Methylone
5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT)
Methoxetamine
para-methoxy-N-methylamphetamine (PMMA)
para-methoxyamphetamine (PMA)
AMB-FUBINACA
MDMB-CHMICA
N-Ethylpentylone
5-fluoro-NPB-22
5-fluoro-ADB
NPS in Malaysia
Laboratory Approach
• Limitations in reference standards for confirmation
• Expensive reference standards
• Limited mass spectral databases
• Screening with chromatography technique
• Confirmation with spectroscopy technique
• Further confirmation with structure elucidation technique
Work Flow in analysis of NPS
General Screening (via
GC-MS)
• Method 1: General Drugs
• Method 2: Legal Highs
Confirmation from above screening
(via GC-FTIR, handheld FTIR &
Raman)
Further confirmation (via
LC-MS/MS)
Workflow in laboratory
Constantly changing market
• Rapidly changing products and chemicals.
Legal Status
• Regulation a step behind the market.
• How to ban them all ? (analogue, generic
scheduling ?).
• One drug becomes controlled, three more
appear on the market (cat and mouse game
continues).
Challenges
Analytical Testing
• How do we test for everything ?
• Reference materials are not available quickly
enough.
• Differentiation of isomers.
• Analysis of thermal labile compounds.
• Quality databases
Commercial peer-reviewed data
In-house with retention time data
Correct nomenclature
• Acquisition method capable of performing the
separation of closely related compounds.
• Skilled chemists who know the science and the
market.
Challenges
Analytical Testing (Toxicology)
• Toxicology (urine analysis) is more difficult.
• Metabolites are unknown and standards don’t
exist.
• Most products contain multiple drugs, extremely
complicated to identify metabolites.
Challenges
Substances control under
legislations • Ketamine – Dangerous Drug Act 1952
• Ketum (Mitragynine) – Poison Act 1952
• 25B-NBOMe
• 25C-NBOMe
• MT-45
• AH-7921 Dangerous Drug Act 1952
• U-47700
• 25I-NBOMe
• PMMA
• 5-fluoro-ADB
Substances control under
Malaysia legislations • N-benzylpiperazine (BZP)
• 25B-NBOME
• 25C-NBOMe
• AM-2201
• 25I-NBOMe Poison Act 1952
• Mephedrone
• MDPV
• JWH-018
• Pyrovalerone
1. SWGDRUG
2. NIST11
3. Wiley Designer drug
4. Cayman Chemical Company
5. AAFS
6. Pfleger
7. Your in-house database
8. Dr. Peter Rosner (Designer Drugs Online)
9. RTI (Research Triangle Institute) drug
database
10. Southern Association of Forensic Scientists
Reference Databases
DR.VANITHA KUNALAN
HEAD OF SYNTHETIC DRUG SECTION
NARCOTICS DIVISION,
FORENSIC SCIENCE ANALYSIS CENTRE
DEPARTMENT OF CHEMISTRY, MALAYSIA
03-79853837
Thank you for your attention
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