POISONS AND DRUGS

This topic covers:

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 POISONS

Any substance that has an injurious or

fatal effect when introduced into, or
taken up by a living organism

‘All substances are poisons; there is none that is not a

poison. The right dose differentiates a poison from
a remedy’
Paracelcus (1493-
(1493-1541)

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 Groups of poisons
• Anions
• Corrosive poisons
• Gaseous and volatile poisons
• Metal and metalloid poisons
• Pesticides
• Toxins

Anions
• E.g. Weedkiller, bleaching agents

• The most toxic is cyanide (CN-)-lethal dose of KCN is

2.8 mg per kg of body mass

• Cyanide – produced naturally by bacteria, fungi

and also found in plant e.g., almonds, mangoes,
cassava.

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 Cassava

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Contains cyanogenic glucoside

Corrosive poisons
• Those that can cause destruction of the body
tissues upon contact (but do not absorb)
• The sensation and injury caused by contact with a
corrosive resembles a burn injury.
• The resultant damage is determined by
– Concentration nature of the substance
– Length of contact time
• Common corrosive includes acids and alkalis e.g.
chromic acid, hydrogen fluoride.
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 Gaseous and volatile poisons
• E.g. CO, HCN
• CO is colourless, odourless and extremely
toxic
• React with hemoglobin therefore reduced
the oxygen level in blood- lead to
asphyxia

– In december 2008, 11 schoolgirls die of

carbon monoxide poisoning after
lighting a fire to keep warm as
freezing temperatures hit China 9

Metal and metalloid poisons

• E.g. Arsenic, mercury, lithium
• Historically, is was normally used for murder to
avoid suspicion
• Now, very rare due to its persistence in the body
after death

Around 1790, Johann Mertzger discovered arsenic

contained substances detection called Arsenic
Mirror method
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 Pesticides
• E.g. DDT, paraquat, organophosphorus
• Involved in homicide, suicide and accidental cases
• in the developing countries, it is pesticides which
have generated large-scale fatal poisoning cases

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 Toxins
• Any poisonous substance that is naturally produced by
an organism (animal, plant, fungus or microorganism)
• E.g. venom, tetrodotoxin (puffer fish), botox
(microbial)
• One important subgroup is alkaloid- atropine (found
in deadly nightshade)-used as recreational drug,
medicine, cosmetic.

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Belladonna
• Devil's Berries, Death Cherries
or Deadly Nightshade

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Belladonna
• Used as cosmetics, medicine, recreational drugs, poisons
and “flying ointment” ingredient.

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Psilocybin ‘Magic’
Mushroom

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Kratom

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• "Kratom makes people feel pain free, strong, active
and optimistic," according to the Website Kratom.com.

• It has multiple functions,

– as a strong and reliable herbal painkiller, to relieve
depression
– as a social and professional enhancer to intensify
communicational skills and induce higher motivation.

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DRUGS
• A substance, when ingested, is capable of
inducing a physiological change.

• Drug can be ingested by

– Swallowing (oral administration)
– Injection (intravenous administration)
– Inhalation/mucous membrane contact
– Absorption through skin

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 Drug or Medicine?
• Drugs are used to treat or prevent disease
• Medicines are combination of drugs and inert
ingredients.
Eg. Paracetamol, Aspirin, diazepam

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• In ancient time, marijuana and related preparations were

used to treat gout, malaria, constipation and rheumatism.
• In modern time, it is useful to treat glaucoma, anorexia
and nausea assoc. with chemotheraphy.

• Another example: Coca Cola

– Was invented by chemist, John S. Pemberton as medicinal drink.
– It was based on coca extracts and the kola nut.
– By 1929-cocaine has been removed from the formula due to its
potential addiction.

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 Drugs Classification
• Drugs can be classified by:
– Origin and function
– General Effect
– Use

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1. Origin and Function

• How it was obtained?

– Natural product. E.g. alkaloids (opiate, caffeine,
cocaine, marijuana
– Semi synthetic E.g. Heroin, steroids
– Synthetic E.g. diazepam (Valium®)

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 2. General Effect

• Forensic chemist categorize drugs on the basis

of the physiological consequences:
– Analgesics
– Depressants
– Hallucinogens
– Narcotics
– Stimulants

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Analgesics
• Drugs that relieve pain
• E.g. Aspirin, ibuprofen, morphine.
• Aspirin reduces pain by inhibiting the pain inducing
event
• Morphine intercepts the pain signal after it is
produced
• Why morphine is addictive and abused?
– Morphine produces pleasurable sensations and euphoria

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 Depressants
• Drugs that depress functions of the CNS.
• Lower the heartbeat, reduced anxiety and promote
sleep.
• E.g. Ethanol and benzodiazepines.

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Hallucinogens
• Drugs that alter the perception of time and reality
• Movement, thought, perceptions, vision and hearing
are also affected.
• E.g. Marijuana, ecstasy

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Cannabis

• Comes in different forms:

– Herbal cannabis/marijuana-
contains lowest concentration of
THCs
– Cannabis resin/hashish-
moderate THCs, usually
supplied in the form of slab or
cakes
– Cannabis oil/hashish oil/hemp
oil-highest conc. Of THCs and
supplied as tar-like substances29

THC

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 Narcotics
• Narcotic drugs have analgesic effects and tend
to depress the CNS and promote sleep
• E.g. Drugs derived from the opium plant,
morphine, codeine, heroin
• Morphine- got its name from ‘morpheus’-Greek
god of dream.

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Opium

• Is a dried latex collected

from field poppy
• Unripe seed capsules is
slitted, allowing the bitter
milky liquid to exude, dry and
oxidise in the sun
• Also, clandestinely cultivated
• Morphine is isolated from
opium and reacted with
acetic anhydride to produce
heroin
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 Chemical structure of Diamorphine
•main active component in heroin
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Preparation of
Heroin from opium

• Each step in the process

contributes constituents
that can be useful in
profiling
• Diluents, adulterants and
impurities can be
identified and
compared to the origin

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 Trivia..
• Which one is more potent?
– Heroin or morphine
• Heroin-
– enters the brain more easily
– More intense ‘rush’ or ‘high’
– Smoked (‘chasing the dragon’) or injected
(dissolved in water)
– Illegal heroine was mixed with glucose, chalk,
flour, talcum- not soluble in water-damage to
blood vessel)

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Stimulants
• Drugs that stimulate function of the CNS,
induces alertness and interferes with sleep.
• E.g. Amphetamine, methamphetamine,
cocaine.
• At high doses, many stimulants are
hallucinogens

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 Coca

Chemical structure of
cocaine

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Types of cocaine and its

adverse effects
• Coca leave- can be chewed to appease hunger,
suppressing fatigue
• Cocaine hydrochloride-is usually snorted, injected,
swallowed
• Crack cocaine (free base cocaine)-usually smoked.
This leads to rapid onset and shorter duration
• Adverse effect-stroke, renal failure and respiratory
arrest

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 3. Use
• Some drugs are grouped on the basis of how
they are used/abused
– Predator Drugs
– Club Drugs
– Human-Performance Drugs
– Inhalants

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Predator Drugs
• Also known as date-rape drugs/drug-facilitated sexual
assault (DFSA)/Drug-facilitated crime assault
• E.g. Alcohol, ketamine, flunitrazepam
• Flunitrazepam (Roofie)
– colourless, odourless and tasteless tablet.
– ready solubility in the victim’s drink and rapid onset of action,
i.e. approximately 15-20 minutes after administration, and the
effect lasts about 4 to 6 hours
– The victim also has a problem in recalling the assault because
of the drug amnesic effect (retrograde amnesia).

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 Club Drugs

• Used at parties and club

• E.g. MDMA (ecstasy, methamphetamine)
• Popular because of the misconception that the
club drugs are less dangerous than such as
cocaine and heroin
• Ecstasy and water toxicity fatal

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Human-Performance Drugs
• Drugs that improve or impair one’s
performance
• E.g. Anabolic steroids and Alcohol

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 Inhalants
• Drugs/substances that are inhaled to produce
their desired effects
• E.g. Paint thinners, Nitrous oxide (laughing
gas)
• These substances give depressant effects
similar to those alcohol.

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Analysis of Drugs and Poisons

• The analysis of a sample for drugs/poisons aims

to provide information of:
– The chemical identity of the drugs/poisons
– The concentration of such substances
• The concentration will establish whether the level of such
substances in the sample is consistent with therapeutic
administration , intoxication or death
• E.g. It can establish the concentration of ethanol in blood
sample-is it exceeds the legally permissible limit (80
mg/100mL)?
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 Qualitative Analysis
• Chemical analysis concerned with establishing
the identity of the analyte
– Observations
– Presumptive tests
– Simple separation techniques-TLC, Paper
chromatography

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Observations
• Start with the observation of those physical
properties-colour, morphology, shape, dimension,
manufacturer’s mark

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Ecstasy tablets

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 Presumptive Test

• The most common is colour tests

– Marquis
– Mandelin’s
– Cobalt-isothiocyanate

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i) Marquis Test
• Diamorphine-Dark purple
• Morphine-Mauve or purple
• Codeine- Blue-Purple
• Cocaine – Slight pink/orange
• Amphetamine/meth- orange
• MDA,MDMA and MDEA – Purple-blue
• Benzodiazepines – No change

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 ii) Mandelin’s Test
• Diamorphine- Blue-grey
• Morphine- Blue-grey
• Codeine- Olive green
• Cocaine – Orange
• Amphetamine/meth- No change
• MDA,MDMA and MDEA – No change
• Benzodiazepines – No change

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iii) Cobalt isothiocyanate Test

• Diamorphine- Blue
• Morphine- No change
• Codeine- No change
• Cocaine – Blue
• Amphetamine/meth- No change
• MDA,MDMA and MDEA – No change
• Benzodiazepines – Temazepam gives blue, others no
change

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 iv) Others
• Dillie-Koppanyi test-barbiturates give blue-
violet colour
• Zimmerman Test- benzodiazepines give pink or
red-purple colour.

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Thin-layer chromatography
• A separative technique and provide numerical
data about the drug species (in the form of Rf
values
• E.g. Separation of amphetamine and
methamphetamine

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 53

Pharmacokinetics
• Studies the movement of drug or foreign
substance (a xenobiotic)

• Divided into 4 stages (ADME):

– Absorption
– Distribution
– Metabolism
– Elimination

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 Exposure/Ingestion xenobiotic

Absorption bioavalability

Distribution

Storage Biotransformation metabolism Storage

Elimination 55

Exposure

• Drug or poison can be ingested by

– Swallowing (oral administration)
– Injection
– Inhalation/mucous membrane contact
– Absorption through skin

• The exposure will lead to

– Local damage-irritation, allergic reactions
– Absorption 56

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 57

Absorption

• Absorption occurred when it enters the

general blood circulation of the body
• What happens after the chemicals have been
absorbed?
– It depends on routes of uptake
– Each route has specific purposes,
advantages, and disadvantages

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 Distribution
• Drug is transported to the target sites where
the drug is needed
• After a drug is absorbed into the bloodstream,
it rapidly circulates through the body.
• As the blood recirculates, the drug moves from
the bloodstream into the body's tissues.

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By mouth

Other
tissues
and
organs

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 • Drugs that dissolve in water (water-soluble
drugs), tend to stay within the blood and the
fluid that surrounds cells (interstitial space).
• Drugs that dissolve in fat (fat-soluble drugs),
such as the anesthetic drug halothane, tend to
concentrate in fatty tissues.
• Other drugs concentrate mainly in only one
small part of the body (for example, iodine
concentrates mainly in the thyroid gland)
• Distribution of a given drug may also vary from
person to person
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By Inhalation

• Lungs have a huge

surface area
• In human, this area ≈
area of tennis court
• Volatile chemical
(solvents, gases) will
pass easily into the blood
• Small particles inhaled,
may be absorbed into the
blood or simply stayed in
lungs cell Air sacs

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 Metabolism
• Some drugs are chemically altered by the body
(metabolized).
• Metabolites may be inactive, or they may be similar
to or different from the original drug in therapeutic
activity or toxicity.
• Some drugs, called prodrugs, are administered in
an inactive form, which is metabolized into an active
form.
• Metabolites may be metabolized further instead of
being excreted from the body. The subsequent
metabolites are then excreted. 63

Metabolism of oral drugs

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 Elimination
• the removal of the drug and its metabolites
from the body
– Get rid of noxious substances
– Protect the body
• Most drugs and other chemicals are removed
from the body by the kidneys i.e. filtration
process
• Volatile chemicals are exhaled through lungs
• Some are excreted through bile, intestine and
then faeces. 65

By mouth

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Type of Samples for Drugs/Poisons
Quantitative Analysis
• Conventional
– Blood
– Urine
• Unconventional
– Hair
– Nail
– Vitreous Humor

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Blood
• Whole Blood
• Plasma-liquid component of blood (minus the
blood cell)
• Serum-refers to blood plasma in which clotting
factors (such as fibrin) have been removed

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 Blood collection kits

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Urine

• is made up of a watery solution of metabolic

wastes (such as urea), dissolved salts and
organic materials
• urine is a liquid collection of metabolic
byproducts
• A range of substances, including ethanol and
drugs/metabolites, are also eliminated from
the body through the urine.

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 Hair

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DRUGS IN HAIR

» Ingested drugs circulate in a person's bloodstream

which nourishes developing hair follicles.

» Drug/metabolites are deposited in the hair follicle

and entrapped in the core of the hair shaft as it
grows out from the hair follicle.

» Normal growth rates for human hair are

approximately half an inch per month.

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Cont.

»Hair samples are less invasive and easier to collect,

store and dispatch compared to blood and urine
samples.

»Determination of abused drugs in hair samples is

important when dealing with autopsy and drug-
facilitated crime cases especially when commonly
utilized samples such as urine and blood are no
longer appropriate.

»Types of hair-depends on the availability

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 Hair Sampling Procedure

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Nail
• Same with hair-provide longer window of detection

• Toenail is preferred
– less exposed to external contamination
– Slower growth

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Nail-Arsenic poisoning

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Vitreous Humor

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 Cont.

• clear gel that fills the space between the lens and
the retina of the eyeball of humans
• The vitreous is 99% water, but has a viscosity two
to four times that of pure water, giving it a
gelatinous consistency
• The metabolic exchange and equilibration between
systemic circulation and vitreous humor is so slow
compared to general circulation

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Sample Preparation
• Prior to analysis, sample will be prepared or
pretreated
– To simplify the matrix
– Concentrate/dilute
– To derivatize

• Therefore, it will be compatible with the

instrument

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 Cont.
• Sample will be prepared according to:

– The nature/form
– Type of analyte- element? Molecule?
– The analytical technique that is to be
employed

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Common Sample Prep. for

Drugs Analysis
• LLE-liquid-liquid extraction

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 SPE-Solid-Phase
extraction
1. conditioned 2. sample was loaded
through the cartridge

4. eluted
5. eluate evaporated to
3. washed
dryness under nitrogen at
40 ºC and residue dissolved
in 0.1 ml of the initial LC
mobile phase

Analyte
Interfering
components
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 Quantitative Analysis
• The definitive analysis is carried out by
instrumental means
• The technique chosen will depend on nature of
drugs, matrix, the amount/concentration
• GC, LC, UV-vis, etc.
• The data will be reported

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Chromatographic method

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 Gas Chromatography

• In GC, the sample is converted to the vapor

state( if it is not already a gas) and the eluent is
a gas (carrier gas).
• The analyte in the vapor state distributes
between the stationary phase and the carrier
gas.
• The stationary phase is generally a nonvolatile
liquid supported on an inert solid.
• The sample is detected as it emerges from the
column (at a constant flow rate).
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Gas Chromatography
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 GC chromatogram

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HPLC
• High-
High-performance liquid chromatography
(HPLC) is the most widely used analytical
separation techniques.

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 Typical HPLC

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HPLC utilize a liquid mobile phase to

separate the components of the mixture

The mobile phase with the components are
forced to flow through a chromatographic
column

The mixture is resolved into its components

The resolution depends on the extent of
interaction between the solute components
and the stationary phase

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 Comparison
GC
-Based on volatility:
-some compounds – (volatile at
high temperature)
-many non-volatile organics are
analyzed after conversion to a
volatile form (hydroxyl and acid
groups converted to ether/ester)
-making volatile derivatives is time
consuming, often inefficient
( introduces error)
-destructive method
HPLC
-Based on polarity, not volatility
(Better than GC for many
nonvolatile, thermally labile, and
polar materials)
-Water samples injected
directly–no extraction, minimal
preparation.
-Non-destructive method
-Easy to learn and use
-No limit by the volatility or
stability 93
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 95

Validation of method
• The process to confirm that the analytical
procedure employed for a specific test is
suitable for its intended use
• Chromatographic method must be validated
based on:
– Selectivity
– Precision of Rt and peak areas
– Linearity, LOD
– Selectivity with real samples
– Accuracy at diff conc.
– ruggedness 96

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 Calibration for Pancuronium

Peak Area Ratio

2
1.5
1
y = 0.0078x + 0.0065
0.5 2
R = 0.9968
0
0 50 100 150 200 250
Concentration (ppm)
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