Forensic Toxicology: Cracking the Case with Chemistry · PDF file• Forensic toxicology...

•5/11/2016

•1

We will begin momentarily at 2pm ET

Slides available now! Recordings will be available to ACS members after one week.

1 Contact ACS Webinars ® at [email protected]

www.acs.org/acswebinars

Type them into questions box!

2

“Why am I muted?”

Don’t worry. Everyone is

muted except the presenter

and host. Thank you and

enjoy the show.

Contact ACS Webinars ® at [email protected]

Have Questions?

•5/11/2016

•2

Have you discovered the missing element?

3

Find the many benefits of ACS membership!

http://bit.ly/ACSjoin

Benefits of ACS Membership

4 http://bit.ly/ACSjoin

Chemical & Engineering News (C&EN) The preeminent weekly news source.

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.

•5/11/2016

•3

5

Let’s get Social…post, tweet, and link to ACS Webinars during today’s broadcast!

facebook.com/acswebinars

@acswebinars

Search for “acswebinars”

and connect!

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

6

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.”

Amy Naylor, N.D.

Biology & Chemistry Instructor

Mitchell Community College

Quote in reference to: http://bit.ly/ChemDeath

•5/11/2016

•4

7


@acswebinars

youtube.com/acswebinars

Search for “acswebinars” and connect!

8

Learn from the best and brightest minds in chemistry!

Hundreds of webinars presented by subject matter experts in

the chemical enterprise.

Recordings are available to current ACS members one week

after the Live broadcast date. www.acs.org/acswebinars

Broadcasts of ACS Webinars continue to be available to the

general public LIVE every Thursday at 2pm ET!

®

www.acs.org/acswebinars

•5/11/2016

•5

ChemIDP.org

Upcoming ACS Webinars www.acs.org/acswebinars

10

®


Thursday, May 19, 2016

Design of Deliverable Macrocycles Session 5 of the 2016 Drug Design and Delivery Symposium

Scott Lokey, Professor of Chemistry & Biochemistry, UC Santa Cruz

Nicholas Meanwell, Executive Director, Bristol-Myers Squibb

Thursday, June 9, 2016

Ice Cream Chemistry

Rich Hartel, Professor of Food Engineering, University of Wisconsin-Madison

Maya Warren, Food Scientist, Cold Stone Creamery

•5/11/2016

•6

11

www.acs.org/acswebinars www.acs.org/acswebinars Slides available now! Recordings will be available to ACS members after one week

Forensic Toxicology: Cracking the Case with Chemistry

Contact ACS Webinars at [email protected]

Darren Griffin Professor of Genetics, University of Kent, UK

Dr. Jason E. Schaff Forensic Chemist, U.S. Government

UNCLASSIFIED

FORENSIC TOXICOLOGY: CRACKING THE CASE WITH CHEMISTRY

Dr. Jason E. Schaff Forensic Chemist

12

UNCLASSIFIED

05/12/2016

•5/11/2016

•7

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.

UNCLASSIFIED 13

UNCLASSIFIED

05/12/2016

OUTLINE

• What is forensic toxicology?

• Pharmacokinetics / pharmacodynamics

• Analytical methods

• Interpretation of results

• Common drug classes

• Closing thoughts

• Questions

UNCLASSIFIED 14

UNCLASSIFIED

05/12/2016

•5/11/2016

•8

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

=

UNCLASSIFIED 15

UNCLASSIFIED

05/12/2016

COMPLIANCE TESTING

SPECIMENS

• Most often urine

• Sometimes blood, sweat,

hair, or oral fluid

WHAT IS THE QUESTION?

• Using something forbidden?

• Not using something required?

CHALLENGES

• Fast, cheap testing required

• Setting cutoff levels

• Variable urine density

– creatinine normalization

• Conflicting regulations

• People “beating the test”

UNCLASSIFIED 16

UNCLASSIFIED

05/12/2016

•5/11/2016

•9

17

Audience Survey Question

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

ANSWER THE QUESTION ON BLUE SCREEN IN ONE MOMENT

• Urine

• Hair

• Breath

• Blood

• All of the above

DRIVING UNDER THE INFLUENCE

SPECIMENS

• Blood!!

– only way to prove intoxication

• Breath (presumptive alcohol)

• Urine (exposure only)


• Was a per se law violated?

• Potential impairment from

intoxication?

CHALLENGES

• Accurate quantitation critical

• Specimen handling / storage

– especially for ethanol

• Interpretation absent per se

• Many specialized attorneys

UNCLASSIFIED 18

UNCLASSIFIED

05/12/2016

•5/11/2016

•10

DRUG-FACILITATED ASSAULT

SPECIMENS

• Blood ideal, but often

collected too late

• Urine most common

• Hair increasingly useful


• Was a person chemically

incapacitated?

• Possible chemical impairment of

short-term memory?

CHALLENGES

•Extremely low LODs required

•Huge (& weird) analyte list

•Complex pharmacological

interpretation

•Educating contributors

UNCLASSIFIED 19

UNCLASSIFIED

05/12/2016

POST-MORTEM TOXICOLOGY

SPECIMENS

• Everything but the kitchen sink!

• Blood, urine, bile, vitreous

humour, liver, brain, etc


• Was there a chemical cause

of, or contribution to, death?

• Could insurance claims or

criminal charges be affected?

CHALLENGES

• Huge target analyte list

• Huge range of concentrations

• Putrefaction

• Post-mortem redistribution

• Pharmacological meaning

UNCLASSIFIED 20

UNCLASSIFIED

05/12/2016

•5/11/2016

•11

PHARMACOKINETICS (PK)

• What does the biological system do to the toxicant?

– Adsorption

(How does it get in?)

– Distribution

(Where does it go?)

– Metabolism

(How does the system try to detoxify it?)

– Excretion

(How does the system get rid of it?)

CO

NC

EN

TR

AT

ION

TIME

1st Order Kinetics

Zero Order Kinetics

2 Compartment Model

UNCLASSIFIED 21

UNCLASSIFIED

05/12/2016

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

UNCLASSIFIED 22

UNCLASSIFIED

05/12/2016

•5/11/2016

•12

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

UNCLASSIFIED 23

UNCLASSIFIED

05/12/2016

24


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

•5/11/2016

•13

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.

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.

UNCLASSIFIED 25

UNCLASSIFIED

05/12/2016

MASS SPECTROMETRY

• Only common detection technique providing unambiguous

identification

• Not a “magic bullet”; know the limitations

– 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

UNCLASSIFIED 26

UNCLASSIFIED

05/12/2016

•5/11/2016

•14

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?

UNCLASSIFIED 27

UNCLASSIFIED

05/12/2016

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

UNCLASSIFIED 28

UNCLASSIFIED

05/12/2016

•5/11/2016

•15

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

UNCLASSIFIED 29

UNCLASSIFIED

05/12/2016

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

UNCLASSIFIED 30

UNCLASSIFIED

05/12/2016

•5/11/2016

•16

31


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

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

UNCLASSIFIED 32

UNCLASSIFIED

05/12/2016

•5/11/2016

•17

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”

UNCLASSIFIED 33

UNCLASSIFIED

05/12/2016

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

UNCLASSIFIED 34

UNCLASSIFIED

05/12/2016

•5/11/2016

•18

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

UNCLASSIFIED 35

UNCLASSIFIED

05/12/2016

STIMULANTS

• Cocaine

– Both enzymatic and non-enzymatic metabolism

– Strong tolerance effects

• Phenethylamines

– Wide range of chemical structures and additional effects

• Pure (almost) stimulant (methamphetamine)

• Decongestant (pseudoephedrine)

• ADHD treatment (methylphenidate)

• Halucinogens (MDMA / “ecstasy”, cathinones / “bath salts”)

UNCLASSIFIED 36

UNCLASSIFIED

05/12/2016

•5/11/2016

•19

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.

UNCLASSIFIED 37

UNCLASSIFIED

05/12/2016

38






•5/11/2016

•20


39

®







Ice Cream Chemistry



40






•5/11/2016

•21

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

41

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.”

Amy Naylor, N.D.

Biology & Chemistry Instructor

Mitchell Community College

Quote in reference to: http://bit.ly/ChemDeath

42


@acswebinars

youtube.com/acswebinars

Search for “acswebinars” and connect!

•5/11/2016

•22

Benefits of ACS Membership

43

http://bit.ly/ACSjoin

Chemical & Engineering News (C&EN) The preeminent weekly news source.

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.

44

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.

®


•5/11/2016

•23


45

®







Ice Cream Chemistry



Forensic Toxicology: Cracking the Case with Chemistry · PDF file• Forensic toxicology...

Documents

Transcript of Forensic Toxicology: Cracking the Case with Chemistry · PDF file• Forensic toxicology...