Forensic Toxicology: Cracking the Case with Chemistry

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Forensic Toxicology: Cracking the Case with Chemistry

Dr. Jason E. Schaff

Darren Griffin

Forensic Chemist, U.S. Government

Professor of Genetics, University of Kent, UK

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UNCLASSIFIED

FORENSIC TOXICOLOGY: CRACKING THE CASE WITH CHEMISTRY

Dr. Jason E. Schaff Forensic Chemist

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DISCLAIMER All opinions expressed or implied herein are those of the speaker. None of them represent, in any way, official positions of the of the United States Government or any agency thereof.

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OUTLINE • What is forensic toxicology? • Pharmacokinetics / pharmacodynamics • Analytical methods • Interpretation of results • Common drug classes • Closing thoughts

• Questions

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WHAT IS TOXICOLOGY? • From dictionary.com: • the science dealing with the effects … of poisons

• “Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.” – Paracelsus

• Interface of pharmacology and analytical chemistry

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COMPLIANCE TESTING • •

• •

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SPECIMENS Most often urine Sometimes blood, sweat, hair, or oral fluid

CHALLENGES • Fast, cheap testing required • Setting cutoff levels • Variable urine density

WHAT IS THE QUESTION? Using something forbidden? Not using something required?

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– creatinine normalization

• Conflicting regulations • People “beating the test”

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Audience Survey Question ANSWER THE QUESTION ON BLUE SCREEN IN ONE MOMENT

Which specimen can be used to PROVE that a person is intoxicated? • Urine

• Hair • Breath • Blood • All of the above

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DRIVING UNDER THE INFLUENCE •

SPECIMENS Blood!!

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Breath (presumptive alcohol) Urine (exposure only)

– only way to prove intoxication

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CHALLENGES Accurate quantitation critical Specimen handling / storage – especially for ethanol

• •

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WHAT IS THE QUESTION? Was a per se law violated? Potential impairment from intoxication?

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Interpretation absent per se Many specialized attorneys

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DRUG-FACILITATED ASSAULT SPECIMENS Blood ideal, but often collected too late Urine most common Hair increasingly useful

• • •

CHALLENGES •Extremely low LODs required •Huge (& weird) analyte list •Complex pharmacological interpretation •Educating contributors

WHAT IS THE QUESTION? Was a person chemically incapacitated? Possible chemical impairment of short-term memory?

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•

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POST-MORTEM TOXICOLOGY • •

SPECIMENS Everything but the kitchen sink! Blood, urine, bile, vitreous humour, liver, brain, etc

WHAT IS THE QUESTION? • Was there a chemical cause of, or contribution to, death? • Could insurance claims or criminal charges be affected?

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• • • • •

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CHALLENGES Huge target analyte list Huge range of concentrations Putrefaction Post-mortem redistribution Pharmacological meaning

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PHARMACOKINETICS (PK)

CONCENTRATION

• What does the biological system do to the toxicant?

– Adsorption (How does it get in?)

– Distribution (Where does it go?)

1st Order Kinetics Zero Order Kinetics 2 Compartment Model

TIME

– Metabolism (How does the system try to detoxify it?)

– Excretion (How does the system get rid of it?)

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PHARMACODYNAMICS (PD) • What does the toxicant do to the biological system? • Desired Effects – Treat disease or symptom – Antidote to another toxicant – Change in mental state

• Undesired Effects – Damage to healthy tissue – Functional impairment – Change in mental state

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PHARMACOGENOMICS • How does an individual’s genetic profile affect PK and PD? • e.g. metabolism of ethyl alcohol – Ethanol + ADH  Acetaldehyde (toxic) – Acetaldehyde + ALDH  Acetate (fuel) – ALDH underproduction = “Asian flush” response to alcohol

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Which of the following analytical techniques is considered a “rising star” in forensic toxicology? • Immunoassay • Gas Chromatography

• Liquid Chromatography • Gas Chromatography Mass Spectrometry • Liquid Chromatography Mass Spectrometry

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ANALYTICAL TECHNIQUES • IMMUNOASSAY • Antibody binding test with colorometric detection • Fast, cheap, simple, but very little specificity

GAS CHROMATOGRAPHY •Robust, mature technology •Very high peak capacity •Limited by analyte thermal stability and volatility •GC-MS is a “Gold Standard” in forensic toxicology.

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LIQUID CHROMATOGRAPHY •Works for almost all polar compounds •Tolerant of “dirty” samples •Problems with very non-polar compounds •LC-MS is a “Rising Star” in forensic toxicology.

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MASS SPECTROMETRY • Only common detection technique providing unambiguous identification • Not a “magic bullet”; know the limitations – – – – – –

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Libraries suggest; standards confirm No identification without fragmentation Uniform procedures for data interpretation Similar spectra within compound classes At least two dimensions of overall data required High resolution ≠ accurate mass

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INTERPRETATION • What is the question? • What is the scenario? • Presence / Absence? – Absence is usually definitive. – Mere presence less so.

• Concentration – Per se limits – Therapeutic vs. toxic vs. fatal – Measurement uncertainty

• Does the answer make sense? 27

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TOLERANCE • Pharmacokinetic – Increased enzyme activity due to toxicant exposure – Higher dose needed to obtain a given concentration

• Pharmacodynamic – Altered receptor / messenger activity due to exposure – Higher concentration needed to obtain a given effect

• Dependence – Special case of pharmacodynamic tolerance – Toxicity or impairment from too low a level

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DRUG-DRUG INTERACTION • Pharmacokinetic – Toxicant competition for available enzymes – Increased enzyme activity from toxicant exposure – Effects on renal clearance

• Pharmacodynamic – (de)Sensitization of receptor systems – Different receptor systems with the same gross effect – Additive vs. synergistic vs. antagonistic

• Drug-Food Interactions – e.g. grapefruit juice 29

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POST-MORTEM REDISTRIBUTION • Chemical Potential Gradient – Biological “pumping” stops

• Gravimetric Gradient – Fluid redistribution

• Trauma – Leakage from rupture of the diaphragm, bladder, or GI tract

• Effect Very Compound-Dependant • Resistant Specimens – Especially vitreous humour

• Great Care Interpreting Concentrations 30

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Which of the following is considered the most common illicit toxicant of forensic interest today? • Ethanol like alcohol

• THC like marijuana • Opioids like morphine • Hypnotic-Sedatives like benzodiazepines • Stimulants like cocaine

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ETHANOL • Most Common Toxicant of Forensic Interest • CNS Depressant – – – –

No single neurotransmitter target Depresses higher functions before lower Euphoria / excitation at lower doses MANY drug-drug interactions

• Per Se Laws – Based on studies of “average” population – Back-extrapolation for determination of violation

• Determination of Impairment and Toxicity – Complicated by very strong tolerance effects 32

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THC • Most Common Illicit Toxicant of Forensic Interest • Extremely Lippophillic; Long Detection Half-Life • Pharmacodynamics difficult to classify – Cannabinoid-specific receptor systems (CNS and peripheral) – Dosing rate and route of administration matter – Hysteresis between effect and blood concentration

• “Synthetic Cannabinoids”

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OPIOIDS • Clinically as Analgesics, Antitussives, Anesthetic Aids • Morphine and Derivatives – From opium poppies; used for thousands of years – Complex PK and PD; extensive interconversion – Severe tolerance and dependence effects

• Synthetic Opioid Agonists – Fentanyl, tramadol, methadone, etc.

• Opioid Antagonists – e.g. naloxone; antidote for heroin overdose

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HYPNOTIC-SEDATIVES • CNS Depressants – Sleep aids, antidepressants, anti-seizure, anesthetic aids

• Barbiturates (direct) – No longer common (overdose risk and dependence)

• Benzodiazepines (indirect) – Extremely common prescription drugs – Complex metabolism and wide range of effects

• Common in Drug-Facilitated Assault

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STIMULANTS • Cocaine – Both enzymatic and non-enzymatic metabolism – Strong tolerance effects

• Phenethylamines – Wide range of chemical structures and additional effects • • • •

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Pure (almost) stimulant (methamphetamine) Decongestant (pseudoephedrine) ADHD treatment (methylphenidate) Halucinogens (MDMA / “ecstasy”, cathinones / “bath salts”)

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CLOSING THOUGHTS • Forensic toxicology operates at the interface of pharmacology, and analytical chemistry. • There are many subfields of forensic toxicology, each with its own focus and requirements.

• The analytical tests must be tailored to answer the relevant questions. • Excellent analytical chemistry is no good if the results aren’t interpreted carefully.

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Dr. Jason E. Schaff

Darren Griffin





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Dr. Jason E. Schaff

Darren Griffin





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How has ACS Webinars benefited you?

®

“ACS Webinars provide great tangible examples to share with my students. I am so excited to have this applied case to describe so that pKa can have real meaning for them, great timing and great presentation.” Quote in reference to: http://bit.ly/ChemDeath

Amy Naylor, N.D. Biology & Chemistry Instructor Mitchell Community College

Be a featured fan on an upcoming webinar! Write to us @ [email protected]

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facebook.com/acswebinars @acswebinars youtube.com/acswebinars

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NEW! Free Access to ACS Presentations on Demand® ACS Member only access to over 1,000 presentation recordings from recent ACS meetings and select events.

NEW! ACS Career Navigator Your source for leadership development, professional education, career services, and much more.

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ACS Webinars does not endorse any products or services. The views expressed in this presentation are those of the presenter and do not necessarily reflect the views or policies of the American Chemical Society.


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Forensic Toxicology: Cracking the Case with Chemistry

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