FS938 Exam

natural drugs

active ingredients and secondary metabolic products of plants or other living systems, which may be isolated by extraction. often consumed in natural form

eaten, chewed, smoked, brewed

cannabis, coca, papaver somniferum (poppy)

Semi-synthetic drugs

products from natural sources that have undergone a chemical process. plant materials, bacterial or cell culture. can be ingested in natural form. large/complex molecules. morphine, cocaine

Synthetic drugs

artificially manufactured substances, which are often produced in clandestine labs or drug manufacturers and destined for the illicit market

synthetic cannabinoids, amphetamines, synthetic opioids

Designer drugs

substances whose molecular structure has been modified to both optimise their effects and circumvent regulatory controls

Evolution of designer drugs

synthetic morphine

70-80s: synthetic variations of fentanyl & phencyclidine (PCP)

80-00s: synthetic variations of amphetamines & phenethylamines (MDMA, AMT, methcathinones)

2010: methylmethcathinones (mephedrone) other legal highs

2016: legislation to combat legal highs or “NPS”

Depressants

slow down CNS, impair reflexes and hand-eye coordination, reduce inhibitions. e.g. alcohol, valium. pain relief

Narcotics

slow down CNS, provide pain relief, supress the cough reaction. e.g. opiates (codeine, morphine), methadone

stimulants

speed up CNS, euphoria, anxiety, increased heart rate and blood pressure. e.g. caffeine, tobacco, cocaine, methamphetamine

hallucinogens

mix up CNS, hallucinations, alters time perception, affects short term memory, increased appetite. e.g. LSD, psilocybin, cannabis

psychoactive substance

any substance capable of producing a psychoactive effect and is not an exempted substance. must be identified, be psychoactive and have identified intent

representative sampling

all variation within population is reflected. may be by characteristic (size, shape, colour, markings)

random sampling

each item has equal chance of being sampled. can be sampled with or without replacement

Cannabis Sativa production

produced illicitly worldwide, indoor/outdoor. most widely used drug. native to mountainous areas of central and south asia

marijuana

dried flowering tops of plants. may contain stalks, seeds etc

cannabis resin

produced in glandular trichomes, especially on female plants

hash oil

produced by solvent extraction of plant material

seized cannabis samples

live plants seized during a house raid, live plants at a growing site, dried plant material, smoked plant material (unicellular trichomes remain in the material after smoking)

hydroponic growth

growing plants without soil using aqueous nutrient solutions. require light - high intensity discharge lights. faster growth. growth of female plants → more glandular trichomes → higher delta 9 THC conc

cannabis plant leaves

palmate with serrated edges

trichomes

the leaves, stalks and flowers are covered in hairs which produce a sticky residue and characteristic odour

cannabis resin

glandular trichomes produce a resin, which is scraped from the surface of the plant and pressed into blocks

hash oil

extraction of cannabis plant with suitable organic solvent (e.g. petroleum or ether) under reflux. once desired strength is obtained, solvent is evaporated and oil concentrated. sticky green, olive or brown residue

cannabis presumptive test

duquenois levine colour test

extract drug into 2.5ml acetaldehyde in 100ml 95% EtOH

add equal vol HCL & add chloroform

THC turns purple in lower organic phase

Problems with cannabis HPLC analysis

resolution, compounds with similar chromatographic appearance, short column life

cocaine

naturally occurring alkaloid present at approx 0.7-1.1% by weight in coca leaf

coca leaf

erythroxylum species of plant. often chewed or brewed

cocaine base

extracted from coca leaves. off white powder/chunks

cocaine hydrochloride

chemical conversion of cocaine base. white powder

Growth of coca plant

colombia, peru, bolivia

Receiving ports for cocaine

Belgium, Netherlands, Spain

Presumptive colour test for cocaine

Cobalt II Thiocyanate or “Scott Test”

Cocaine HPLC analysis

alkaloids dont chromatograph well. mobile phase is modified phosphate buffer

Cocaine FTIR analysis

can distinguish cocaine base from HCl. problematic with complex mixtures

cocaine NMR analysis

different solvents needed for base vs HCl. quantitative. structure elucidation

cocaine GCMS analysis

most common. base or HCl easily dissolved in solvents

an internal standard must not:

co-elute, react or catalyse decomposition, exhibit poor chromatographic behaviour

solvent profiles to determine where base to HCl conversion took place:

Colombian → mixed acetates

Peruvian → acetone, clean ethyl acetate

Bolivian → ether

Poppy Cultivation (growth)

Afghanistan (>80%), “Golden Triange” (Myanmar, thailand, laos), mexico, colombia

raw opium

complex mixture containing sugars, proteins, lipids, water, and active alkaloid compounds (10-20%)

alkaloid

nitrogenous organic compound of plant origin which have physiological effects on humans

diamorphine content

morphine, codeine and small amount of noscapine and papaverine

diamorphine is a…

narcotic analgesic

Heroin

mixture of compounds (in the UK). street sample of diamorphine and all other cutting agents or impurities

common adulterants

paracetamol, caffeine, lidocaine, aspirin, fentanyl

common diluents

starches and sugars

heroin sample types

poppy extracts, raw opium, prepared morphine, powdered diamorphine/heroin

heroin FTIR analysis

can distinguish between base and HCl. problematic with mixtures or low quality samples

heroin NMR analysis

different solvents needed for base and HCl. quantitative, structure elucidation. limitations: sample degradation and adulterants

heroin HPLC analysis

common. elution order based on polarity. basic compound so mobile phase is modified with base. diamorphine chromatographs well, morphine doesnt

heroin GCMS analysis

can de-acetylate to monoacetylmorphine or morphine if paracetomol is present

Amphetamine Type Substances (ATS)

group of synthetic substances comprised of amphetamine-group (amphetamine, methamphetamine and methcathinone) and ecstasy-group substances (MDMA and analogues)

analogue

a compound with a molecular structure closely similar to that of another.

phenethylamine

parent compounds of ATS

common amphetamine derivatives

amphetamine, methamphetamine, MD, MDMA, MDEA

presumptive colour test for ATS

mandelin - green

maquis - brown/orange/green. black for MDMA

derivatisation of ATS

derivatisation (with CS2) or base extraction (with ammoniacal CHCl3). reduces polarity. improves chromatographic behaviour. characteristic ion fragments

Leuckart Synthesis

synthesis: BMK + formamide → amphetamine base

separation: sodium hydroxide separates crude base oil

purification: oil purified by distillation or solvent extraction

crystallisation: sulfuric acid makes amphetamines sulfate

packaging: filtering, drying, adulteration, tableting

Amphetamine or methamphetamine precursor

benzyl methyl ketone (BMK) or phenylacetone (P2P)

MDMA and MDA precursors

piperonyl methyl ketone (PMK) or MDP 2P

nitrostyrene synthesis

formation of nitrostyrene then lithium reduction

mixing benzaldehyde with nitroethane in ammonium acetate in acetic acid and reflux to form nitrostyrene. purified with EtOH, reduced with LI(AlH4), free base extracted with ether and precipitates as sulphate salt with H2SO4

Reductive amination

ketone reacted with ammonia to form imine. reduced under high temp and pressure to form the amine

level D PPE

not usual for clan labs unless no contaminants. more for daily lab work. repellent coveralls, a mask and safety glasses

Level C PPE

when the concentration and type of airborne contamination is unknown. hooded chemical resistant overalls and air purifying respirator

cocaine extraction/heroin processing lab

Level B PPE

where theres a need for high respiratory and skin protection. e.g. ambient atmospheric vapours or gas levels, hazardous waste sites, oxygen deficient environment

positive pressure, full facepiece, hooded chemical resistance suit and boots

ATS synthesis lab

Level A PPE

where theres greatest potential for hazards. e.g. transdermal or severe inhalation.

fully encapsulated chemical and vapour protective suit with a full face SCBA

LSD or fentanyl labs

Methamphetamine clan labs

“one pot” operations. reaction vessel in plastic bottle. materials purchased at hardware stores & pharmacies. solvents/fuel, cold packs, Li batteries, pseudoephedrine

Crystal Meth/Ice clan labs

larger scale. usually P2P as precursor. crystal extraction may be at secondary site. flammability risk. acetone, sieves, fans, buckets/containers

Amphetamine clan labs

large scale, various synthesis routes. precursors commonly found onsite. reaction vessels, reflux apparatus, precursors, finishing products

extraction clan labs

large scale cocaine extraction from unusual matrices. cocaine base to HCl. cement mixers, solvents, presses, packaging materials

tableting operation clan labs

may be small or large scale. associated with many illicit substances, incl. ATS and synthetic opioids. inhalation hazards. tablet presses, cutting agents, scales

Clan lab Sampling

all reactions safely turned off. reaction vessels, finished products and precursor products should be samples. sampling by attributes or hypergeometric distribution strategy

Hazards in clan labs

fire/explosion, inhalation, oxygen-deficient atmosphere, trips and falls

Evolution of NPS

1990s: phenethylamines/piperazines

2004: synthetic cannabinoids

2005: early warning system

2008: SMART programme

2010: synthetic cathinones

2015: synthetic opioids

NPS subgroups

cannabinoid receptor agonist, sedative/hypnotic, dissociative, stimulant, hallucinogen, synthetic opioid

Cathinones

closely related to phenethylamine family. active ingredient in the leaves of the khat plant. cotton

NPS opioids

highly potent, synthetic substances that act on the same targets as natural opioids to produce pain relief. some have legit medical use. many more potent than morphine

Ion Mobility Spectrometry for NPS

rapid screening method, screens the surface of synthetic cannabinoids, positive or negative mode, needs further testing

GCMS for NPS

most common for identification of synthetic cathinones and other NPS. standards available for some

HPLC for NPS

reverse phase chromatography used for synthetic cathinone ID. LC-MS/MS for increased sensitivity

NMR for NPS

structural elucidation of new compounds or analogues. discrimination of positional isomers. quantitative

High Resolution Mass Spectroscopy info

accurate molecular mass

Mass Spectroscopy info

fragmentation pattern

Nuclear magnetic Resonance (NMR) info

structure elucidation

Ion mobility spectroscopy info

rapid screening

UV-VIS info

absorbance peaks and shifts

FTIR info

differentiate isomers

colour of synthetic cannabinoids using fast blue B

orange/red

dose

quantity of a chemical introduced into a biological system per unit time

threshold value

dose which most therapeutic/recreational drugs will be found at

the stronger the substance, the ____ the dose-response curve

steeper

the steeper the dose-response curve…

the quicker the rise in response

Factors which affect the response and shift the curve

tolerance, polydrug use, drug interaction, genetics, overall health and age

NOAEL

No observed adverse effect level

NOEL

no observed effect level

LOAEL

lowest observed adverse effect level

LOAL

lowest observed effect level

ED50

effective dose for 50% of those tested

TD50

toxic dose for 50% of those tested

LD50

lethal dose for 50% of those tested

blood as toxicology sample

heart (only when dead) or peripheral. 50-100ml. subdural or epidural clots. may need preservatives