Exam 1- Analytical Forensic Toxicology 470 WVU

Define toxicology (brief)

The study of the adverse effects of chemical agents on a biological system

Define xenobiotic

a molecule or substance that is not normally found in that specific organism

Define forensic toxicology

The science of detecting and identifying the presence of drugs or poisons in body fluids, tissues, and organs

Who was Hippocrates?

The father of Greek medicine

Who was Dioscorides?

Wrote "The Preparation, Properties, and Testing of Drugs"

Who was Maimonides?

Wrote "Poisons and their Antidotes"

Who was Paracelsus?

Considered to be the Father of modern toxicology, and initiated the idea of dose-response

What was Paracelsus' full name?

Phillippus Aureolus Theophratus Bombastus von Hohenheim

What are the components of the Marsh Test? (general use)

sulfuric acid (H2SO4) and Zinc (Zn) to test for the presence of arsenic trioxide (As2O3)

If the Marsh Test was positive for Arsenic?

Arsine Gas (AsH3) would result from protonating the acid. When ignited, it would produce a black film

What are the components of the Marsh Test? (Forensic use)

Take a specimen and heating it with a reducing agent (zinc) in an acid medium will produce bubbles (arsenic trihydride). Black mirror deposit will confirm As

What happened during the Styrian defense?

Peasants consumed As2O3 (300 or 400 mg) every other day

What is a Fowler Solution

it is a potassium arsenite solution that contains 1% potassium arsenite and is dissolved in water

Who was Jean Servais Stas?

developed the first effective method for extracting alkaloids (marijuana) from biological specimens

Who modified the Stas method?

Friedrich Julius Otto worked to isolate higher-purity alkaloids

Who is considered the first forensic toxicologist?

Dr. Alexander Gettler

Who was Dr. Charles Norris, and what was he known for?

NYC Chief ME in 1918, who replaced the Coroner System with the ME system, quoted "justice is done based on Science."

Who was Alice Hamilton?

She was the first woman appointed as a professor at Harvard and a leading expert in the field of occupational health, and a pioneer in the industrial toxicology field

What is a toxicant?

A type of poison made by humans or introduced into the human environment by human activity

What is the basic definition of a drug?

a substance that is used to produce a physiological response in the body

What is the definition of a drug of abuse?

drugs that are used with no medical purpose

Define psychoactive drugs

any substance that alters the normal functioning of the CNS

What is an analgesic?

a drug or substance that lessens or eliminates pain

What is a narcotic?

An analgesic or pain-killer substance that depresses vital body functions such as blood pressure, pulse rate, etc

What is a hallucinogen?

a substance that induces changes in mood, attitude, thought, or perception

What is a depressant?

a substance used to depress the functions of the CNS

What is a stimulant?

a substance taken to increase alertness or activity

What is an anabolic steroid?

A drug taken to promote muscle growth

Examples of biological fluids for toxicology testing:

- urine

- saliva

- blood

- serum

- humus viterous

- billis

- gastric contents

Examples of organs for toxicology testing:

- kidney

- brain

- liver

What is the purpose of the chain of custody?

to guarantee the integrity, preservation, and conservation of the materials submitted as evidence, to know the status of the process where testing material was handled

What are the basic elements of the chain of custody

- sample collection

- reception at the main lab

- opening of the evidence

- report

What is involved in a toxicological analysis?

general drug screening (Immunoassay) and an extraction system for specific matrices (LLE, SPE, QuEChERS)

What is a qualitative analysis?

preliminary identification to assess the presence of the questioned materials in the biological matrix

What is a quantitative analysis?

identification and quantification of the material as present in the biological matrix

What type of testing is done in Human Performance Tox?

- DUI

- Clinical Emergencies

- SA

What does WADA stand for?

World Anti-Doping Agency

What type of testing is done in Post Mortem FS Tox

- accidental poisoning

- drug overdose

- suicidal poisoning

- homicidal poisoning

Why is post-mortem toxicology important?

It helps to determine the cause and manner of death

What is the general approach to drug analysis?

- screening/presumptive

- separation/ purification

- confirmatory testing

- quant if appropriate

- other tests (if needed)

What is the cut-off for amphetamine for GC/MS confirmation? (in ppb)

500 ppb

What is the cut-off for methamphetamine for GC/MS confirmation? (in ppb)

500 ppb

What is the cut-off for cannabinoids for GC/MS confirmation? (in ppb)

15 ppb

What is the cut-off for cocaine metabolites for GC/MS confirmation? (in ppb)

150 ppb

What is the cut-off for opiates for GC/MS confirmation? (in ppb)

2000 ppb

What is the cut-off for codeine for GC/MS confirmation? (in ppb)

2000 ppb

What is the cut-off for 6-acetylmorphine for GC/MS confirmation? (in ppb)

2000 ppb

What is the cut-off for Phenecyclidine (PCP) for GC/MS confirmation? (in ppb)

25 ppb

What is the structure of fentanyl

What is the structure of cocaine

What is the structure of cannabinoids

What is the structure of morphine

What is the structure of methamphetamine

What are the advantages of using blood in toxicology testing?

- widely used

- screening potential unlimited

- detection window is minutes to days

- original sample can be retested

What are the disadvantages of using blood in toxicology testing?

- invasive

- must be stored in the fridge

- Extraction and analysis are more complex due to matrix interference

What are the advantages of using urine in toxicology testing?

- most frequently used

- on-site testing

- Many drugs can be identified

- original sample can be retested

What are the disadvantages of using urine in toxicology testing?

- cheating

- sample handling and storage difficulties

- Interferences are common

What are the advantages of using sweat in toxicology testing?

- tests prospectively

- tamper-proof

- easier to detect the presence of parent drug in heroin, THC, and cocaine cases

What are the disadvantages of using sweat in toxicology testing?

- uses an electrical current to generate sweat

- limited experience

- limited range

- can become environmentally contaminated

What are the advantages of using hair in toxicology testing?

- not possible to cheat

- up to 90 days detection window

- can discriminate between light, moderate, and heavy users

- fewer interference

What are the disadvantages of using hair in toxicology testing?

- limited number of drugs

- fewer providers

- not useful for certain drugs (THC)

- Environmental contamination

What are the advantages of using oral fluid in toxicology testing?

- easy to collect

- cheating difficult

- cost-effective

What are the disadvantages of using oral fluid in toxicology testing?

- fewer databases

- short detection window

- sample handling issues

- individual saliva production

- not sensitive on-site for marijuana

Define toxicity

any adverse effect of a xenobiotic on a biological system; that can express damage to a living system elicited by a chemical of either endogenous or exogenous origin

Define toxin

a xenobiotic of biological origin

Define toxicant

a xenobiotic of manmade origin

Define hazard

The likelihood that a xenobiotic will cause toxicity at a specific dose or exposure level (probability)

Define risk

a quantitative description of hazard

Define safety

The reciprocal of hazard, the likelihood that toxicity will not occur

Define toxic

term used to describe a detrimental or negative impact or effect on subjects

What are local effects in toxicology?

Contact is first made by the toxicant and the biological system by ingestion or inhalation, or irritant material

What are systemic effects in toxicology?

requires the absorption and distribution of a toxicant from its entry point to a distant site where the deleterious effects are produced

What is the difference between a drug and a toxin?

A drug is a beneficial pharmaceutical compound, whereas a toxin is capable of causing an injury

How much nicotine is in one cigarette?

10-12 milligrams (mg)

What is the graph for the dose-response relationship?

concentration (x-axis) v. intensity of response (y-axis)

How do we assess toxicity?

- animal toxicology studies

- controlled clinical studies

- epidemiological studies

What does ADME stand for?

Absorption

Distribution

Metabolism

Elimination/Excretion

Define absorption

The processes by which the drug of poisons are brought into the blood and cells of the body

Define distribution

The process by which drugs and poisons are moved around the body and taken up into the organs and tissues

Define metabolism

The process by which the drugs and poisons are biochemically altered/ broken down

Define elimination

The process by which drugs and poisons are removed from the body

What are the components of a GC/MS system?

Carrier gas - an inert gas (usually helium) that moves the sample through the system.

Injector - where the liquid or gas sample is introduced and vaporized.

Column (inside oven) - separates the compounds based on their chemical properties.

Transfer line - heated pathway that carries compounds from the GC to the MS.

Ion source - turns compounds into charged particles (ions).

Mass analyzer - separates the ions by their mass-to-charge ratio (m/z).

Detector - records the ions and creates a signal.

Computer/data system - processes the signal into a chromatogram and mass spectra for identification.

What are the components of an LC/MS system?

Pump - pushes liquid solvent (mobile phase) through the system.

Injector/Autosampler - introduces the liquid sample.

LC Column - separates compounds based on their chemistry.

Ion Source (ESI) - turns liquid-phase molecules into gas-phase ions.

Mass Analyzer - separates ions by their mass-to-charge ratio (m/z).

Detector - records the ions.

Computer/Data System - processes the signals into chromatograms and spectra.

What is LD 50?

lethal dose for 50% of the test population.

What is ED 50?

effective dose for 50% of the population.

How to find the pH of an acid from a concentration example: 0.2M

- log (0.2M)= pH

How to find [H+] concentration from Ka and concentration example: 0.2M

sqrt(Ka)(0.2M)= [H+]

How to find pH from pOH

pH + pOH= 14

How to approx. for a weak acid HA⇌H++A−

[H+]≈sqrt(Ka)​(concentration)

In water (assuming density ≈ 1.00 g/mL at room temp), ppb relationship

1 ppb = 1 µg/L

10 ppb = 10 µg/L

100 ppb = 0.1 mg/L

A forensic toxicology lab detects 0.050 mg/L of arsenic in a water sample. What is this in ppb?

0.050 mg/L (1000ppb/mL/L)= 50 ppb

Florence Maybrick

Poisoned her husband using arsenic. Used soaked flypapers and arsenic powder mixed with soot, Fowler's solution: K arsenic

Lafarge Murder

Used a cake containing arsenic, Matthieu Orfila best-known forensic toxicologist of the time

Forensic files video

The husband poisoned wife with insect traps and arsenic but small doses actually helped her build tolerance. Found in her hair dating back to certain months

Affected Organs

Hepatoxic = Liver

Nephrotoxic = Kidney

Hematoxic = Blood

Central Nervous System

Schedule 1 drug

High potential for abuse

No currently accepted medical use

lack of accepted safety for use

LSD, Heroin, Marijuana, Methaqualone

Schedule 2 drug

High potential for abuse

Currently accepted medical use with severe restrictions

abuse may lead to severe psychological or physical dependence

Morphine, PCP, Cocaine, Methadone, Methamphetamine

Schedule 3 drug

drugs potential for abuse is less than those in 1 and 2

there is currently accepted medical use in U.S, but abuse may lead to moderate or low physical dependence or high psychological dependence.

anabolic steroids, codeine, hydrocodone, some barbiturates

Schedule 4 drug

low potential for abuse relative to 3

currently accepted medical use

may lead to limited physical dependence or psychological dependence

Xanax, Valium, Darvon

Specimen collection (easy to difficult)

Hair

Nails

Saliva

Urine

Exhale Breath

Breast Milk

Blood

Cord Blood

Tissues