Toxicology

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Toxicology

• Detection and Identification of Drugs and Poisons
  in Body Fluids

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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

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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!

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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
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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
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The Up Side

• A relatively small number of drugs account for
  the majority of toxicology cases
• Alcohol and cocaine account for 90 of analyses

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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

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Classifying Drugs
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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

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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

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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

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Home Drug Tests
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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

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Estimating the Pharmacological Effect

• Age
• Physical Condition
• Tolerance if drug user
• Synergy between drugs
• Alcohol barbiturates produce enhanced effect

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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

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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

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Carbon Monoxide Poisoning
CO displaces O2 from binding sites on the Fe
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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

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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

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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