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Toxicology

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Toxicology. Detection and Identification of Drugs and Poisons in Body Fluids ... Antimony. Mercury. Thallium. Reinsch test. Copper strip in acid solution ... – PowerPoint PPT presentation

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Title: Toxicology


1
Toxicology
  • Detection and Identification of Drugs and Poisons
    in Body Fluids

2
Forensic Toxicology
  • Toxicology in cases involving violations of
    criminal law
  • Drunk Driving
  • 17,500 automobile deaths, 40 alcohol related
  • Most abused drug in Western world
  • Drug Overdose
  • Rapid testing in life/death situations
  • Illegal and abused legal drugs
  • Intentional Poisoning
  • Cause of Death

3
The Big Challenges
  • Small amounts (?g or less) of UNKNOWN substance
    diluted in LOTS of body fluid
  • Substance is dissolved so you cant observe
    physical properties
  • Substance may have metabolized
  • Looking at breakdown products
  • Need to quantify to assess toxicity
  • Tolerance is individual!

4
Heroin Metabolism
  • Heroin is metabolized to morphine
  • Morphine binds to carbohydrates
  • Morphine-carbohydrate complex is eliminated in
    the urine
  • Morphine-carbohydrate complex is detected

Heroin
Morphine
5
Cocaine Metabolism
  • 80 of cocaine is metabolized to benzoylecgonine
    (BZE)
  • BZE excreted in urine
  • BZE extracted using solid phase technique
  • BZE reacted to make a trimethyl silyl derivative
  • The derivative is detected in the mass spec

Heroin
cocaine
Morphine
BZE
6
The Up Side
  • A relatively small number of drugs account for
    the majority of toxicology cases
  • Alcohol and cocaine account for 90 of analyses

7
Extracting Drugs from Body Fluids
  • Most drugs are either acids or bases
  • Acids lose a hydrogen ion
  • Acid drugs are extracted from acidified water
    with chloroform
  • Basic drugs are extracted from basic water
    solutions with organic solvents

8
Classifying Drugs
9
Toxicology in Practice
  • Extract sample with from acidic and basic
    solutions
  • Screening tests
  • Immunoassay
  • Gas chromatography
  • Thin-Layer Chromatography
  • Confirmation test
  • GC-Mass Spectrometry most accepted

10
Toxicology in the Workplace
  • Drug abuse on the job
  • May be part of job application process
  • Urine tests in military
  • Urine tests in professional sports

11
Urine Tests
  • Poor indication of present degree of impairment
  • Urine is formed outside of circulatory system
  • Levels build up over up to 1-3 days
  • Used to corroborate other evidence
  • Balance and coordination tests

12
Home Drug Tests
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products/Integrated20EZ20Drug20Test2010.jpg
http//www.home-drug-urine-test-kits.com/3.jpg
13
Enzyme Multiplied Immunoassay Technique (EMIT)
  • Drug metabolite protein complex (antigen)
    injected into rabbit
  • Rabbit produces antibodies
  • Rabbit blood serum contains antibodies (nearly)
    specific for the drug metabolite
  • Antibodies added to human urine sample
  • Antibodies bind to drug in urine
  • Enzyme labeled drug added to sample sopping up
    excess antibodies
  • Enzyme labeled drug left uncombined is related to
    original amount of drug in urine

14
Estimating the Pharmacological Effect
  • Age
  • Physical Condition
  • Tolerance if drug user
  • Synergy between drugs
  • Alcohol barbiturates produce enhanced effect

15
The Police Drug Recognition Experts
  • Police are trained to recognize degree of
    impairment at a specific time
  • Toxicologist cant infer degree of impairment at
    a specific time
  • Nature of impairment consistent with class of
    drug
  • Toxicologist can identify the specific drug

16
Heavy Metal Poisoning
  • Arsenic
  • Bismuth
  • Antimony
  • Mercury
  • Thallium
  • Reinsch test
  • Copper strip in acid solution
  • Get silvery or dark coating on the copper
  • Confirmation test
  • Atomic absorption
  • Atomic emission
  • X-ray diffraction

17
Carbon Monoxide Poisoning
CO displaces O2 from binding sites on the Fe
18
Detection of CO in the Blood
  • Spectrophotometry
  • Beers Law
  • Absorption spectrum changes
  • Chemical Reaction
  • Liberates CO from hemoglobin
  • Use GC quantitatively to measure amount of CO
    released
  • Measure area under GC peak and relate to standards

http//osulibrary.oregonstate.edu/specialcollectio
ns/coll/pauling/blood/pictures/science13.006.2-spe
ctra.jpg
19
Fatal Doses of CO
  • 280 million hemoglobin molecules/red blood cell
  • 50-60 of Fe sites occupied by CO is fatal
  • Drug interactions increases sensitivity
  • With alcohol, 35-40 CO occupation is fatal
  • Tolerance levels
  • Chain smokers have 8-10 of hemoglobin sites
    occupied by CO

http//www.uhseast.com/134221.cfm
20
Slide 82 of 94
21
Fatal Doses of CO
  • 5-10 minutes of car exhaust in single car garage
  • In arson victims
  • High levels of CO suggest person was alive during
    fire
  • Low levels of CO suggest person was dead before
    fire
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