Forensic Toxicology Final

An illicit drug user taking opioids requires higher doses to reach the same pain relief after a period of usage. This phenomenon is known as?

Tolerance

What items must be present on the Chain of Custody forms according to ASTM guidelines?

Signatures of sampling personnel and signatures of all personnel handling/receiving samples, Preservation of sample with amount and type, Field notes, and Sampling location ID, date, and time interval

What biological specimen type has the shortest detection window for analysis post storage in preservative?

Breath

Which of the following factors influences the LD50 value of a substance?

Species of the test animal, route of administration, age of the test animal, sex of the test animal

Who is referred to as the "father of toxicology" for his contributions to the field?

Paracelsus

What is the best sample preparation technique for this diazepam

Liquid-Liquid extraction using chloroform (CHCl3) as the solvent

What is the most common method of toxicant absorption

Oral ingestion

10 mg of heroin and 10 mg of benzos were taken together resulting in death. Doses of 30 mg of heroin do not induce death and doses of 20 mg of benzos do not induce death. What effect cause increased sedation and respiratory depression that resulted in fatality?

Synergism

A drug with a high volume of distribution is most likely to be?

Lipophilic and widely distributed in tissues

List each area present in the pharmacokinetics acronym ADME

Absorption, distribution, metabolism, elimination

Buprenorphine has a Kd of 0.18 nM for the u-opioid receptor. Naloxone has a Kd of 1 nM. Both work to reduce dependency on opioids through receptor interaction. Determine Ka values of both substance and suggest which interacts with the u-opiod receptor with higher affinity

buprenorphine: 5.6nM^-1

naloxone: 1 nM^-1

buprenorphine has the highest affinity

Consider the following information about drug X: The dose is 150 mg, the absorptivity is 35% the volume of distribution is 25 L and the half-life is 24 hours with first order kinetics. What is the rate constant?

0.0289 hr^-1

LSD LD50 is approximately 0.1 mg/kg and marijuana Ld50 is 9000 mg/kg. Classify these drugs as with highly toxicity, moderate toxicity or low toxicity. Calculate lethal doses (in mg) for a person that weighs 168 pounds (1 pound=0.454 kg)

LSD : high toxicity, 7.63 mg

marijuana : low toxicity, 686448 mg

Beer-Lambert Law in absorption spectroscopy fails at?

High concentrations of absorbing molecules

GHB may not be detectable by GC analysis due to the removal of carboxylic acid with higher temperatures (decarboxylation). To measure these compounds by GC, what technique might be employed.

Derivatizing the structure by adding different functional groups for detection

An antibody developed for an immunoassay test exhibited one binding constant for the analyte tested Ka-10^8. One might classify this antibody type as?

monocolonal

Chromatographic separations of a mixture are based on?

the interaction of the components with both stationary and mobile phases

What is the primary role of ELISA in forensic toxicology

Screening samples for the presence of drugs or their metabolites

What is the primary purpose of a confirmatory test in forensic toxicology?

To eliminate false positives from initial screening test

A main advantage of using HPLC with UV-Vis detection over GC for thermally labile compound detection is

HPLC analyzes compounds that are nonvolatile and/or are unstable as gases

ESI and MALDI belong to which of the following techniques

Ionization

Alcohol is classified as

Depressant

Medication-assisted treatment (MAT) is approved by the FOOD and Drug Administration for opioids. What is a MAT antagonist?

naltrexone

What is a key step in sample preparation required for GC-MC analysis of amphetamine-like compounds

derivatization

Which of the following drugs act on the GABA A receptors in the brain

diazepam

Which is not an effect of stimulants

sleep

delta-THC is befound in the greatest concentrations in which part of cannabis sativa

plant seed and oil extracts

what is the primary enzyme involved in the metabolism of alcohol in the liver

alcohol dehydrogenase

what does not play a role in the blood alcohol content (BAC)

time of day

Log P values of several opioids are given below . Based on this data, which compound would be the most potent opioid?

Morphine : 0.93

Codeine : 1.20

Hydrocodone: 1.34

Nalorphine : 1.87

oxycodone : 2.03

Amphetamine interacts primarily with which receptors?

Dopamine neurotransmitters

Describe the 3 types of cannabinoids

phytocannabinoids (plant THC, CBD), endocannabinoids, synthetic cannabinoids (man made)

What is the reaction order, rate constant, half-life, and volume of distribution for this plot. The total clearance is 1.25 L/hour

Reaction order : 1st

rate constant:0.02014 hr^-1

half-life:3.44 hrs

Volume distribution : 6.2 L

What is the reaction order, rate constant, half-life, and volume of distribution for this plot. The total clearance is 1.25 L/hour

Reaction order : 0th

rate constant: 0.0893 mg/mL*min

half-life: 112 min

Volume distribution : 13.9 L

Consider the structure of methadone (Rohypnol) 1) does it have a high number of potential hydrogen bond donors and acceptors? 2) does it have a high tissue distribution 3) does it have a long half-life 4)is it more likely to be eliminated in urine?

1) yes it has 4 HB and HA

2) yes

3) yes

4) No

Consider the structure of 1,4-butanediol 1) does it have a high number of potential hydrogen bond donors and acceptors? 2) does it have a high tissue distribution 3) does it have a long half-life 4)is it more likely to be eliminated in urine?

1) No

2) No

3) No

4) Yes

which of the following curves illustrates the lowest potency?

Curve D

what is the drug class and schedule (if applicable) for this structure?

Opiates and schedule II

what is the drug class and schedule (if applicable) for this structure?

alcohol and n/a

what is the drug class and schedule (if applicable) for this structure?

benzodiazepines and schedule IV

what is the drug class and schedule (if applicable) for this structure?

cannabanoids and schedule I

describe the pharmacokinetic terms of half-life, volume of distribution, and bioavailability

1) most of the presence for the longest time is in the tissue and fat

2) short-lived in blood or tissues

3) high volume of distribution

3) bioavailability is high as concentration in blood is high

Pharmacokinetics

the study of the time course of drugs in the body

Bioavailability

amount of available substance in the body as a ratio of the amount taken. It is dependent upon many factors including administration method.

Lipophilic drugs crosses the membrane more?

easily

Distribution pathway depends on?

Ability of a drug to move from absorption site to blood

Volume distribution increases when?

There is more distribution to the tissues and lower in blood

Volume distribution decreases when?

there is less distribution to the tissues and higher blood.

Plasma Clearance

Defined as the removal rate of drugs from plasma

Hepatic Excretion

Clearance by the liver in bile.

Carrier protein

transport of ions and small organic molecules across cell membranes that are not sufficiently lipid soluble

Ion Channel

Gateways in cell membranes

Affinity

refers to the strength of binding between a drug and a recptor

Agonist

drug that binds to receptors and initiates a cellular response and has affinity

Antagonist

drug that binds to receptors but cannot initiate a cellular response but prevent agonist from producing a response

Amniotic Fluid

useful for prenatal drug exposure

Meconium

Long-term window of drug exposure, non-invasive, demands sample prep.

Digestion prep technique

removal of organic matter (ex wet digestion, dry, and microwave assisted decompostion)

Filtration

separation of solid from a liquid

Protein precipitation

removal of protein from sample, protein binding interferes with detection

LLE

involves analyte partition between the aqueous phase and organic solvent

Solid Phase Extractions

based on the principle of separation based on affinity consisting of liquid solid separation

Immunoassay

an analytical technique that uses naturally occurring reagents knwon as antibodies to selectively determine sample compnents

are immunoassays expensive or inexpensive

inexpensive

Forensic Immunoassays pros

screening purposes only, rapid and efficient, and covers a broad range of analytes, high sensitivity and specificity

monoclonal

produced by a single cell line, binding w/ the same affinity, expensive

polyclonal

different lines of antibody-producing cells and binding with a range of affinities

ELISA testing

enzyme linked immunosorbent assay

EMIT testing

enzyme multiplied immunoassay technique

ELISA advantages

high sensitivity, less subject to matrix effects, possibility of automation, shelf life is long

ELISA limitations

cost per sample is usually elevates, it cannot be used in samples stored with sodium azide.

EMIT advantages

easy to automate, shelf life long, labelled drug can be measured without separation from free drug, absorbance change as function of time

sensitivity refers to ?

assays ability to detect low concentrations of the analyte

specificity refers to ?

the assays ability to which it can distinguish between different analytes in a solution

sensitivity formula

TP/TP+FN

Specificity formula

TN/TN+FP

Separation is based on?

sample components residing in stationary and mobile phases

Advantages of Gas Chromatography

Good for volatile samples, can be easily automated for injection and data analysis, compounds that are not decomposed at their vaporization temperature

Gas chromatography gas selection depends on?

Column type and detector

GC column type He

high cost, safe to use, wide optimum linear velocity range

GC column type N2

peak broadening in the column, cheaper, safe, low optimum linear velocity and analysis takes more time.

GC column type H2

alternative to He

GC Detectors- Flame Ionizing Detector (FID)

sample leaving the column exist through H2 air flame burning at the jet tip. They’re ionized

GC Detectors- Electron Capture Detector (ECD)

beta particles ionization w/ low electrical resistance and high current between electrodes, compounds with halogens, CN or NO2 groups are well analyzed by GC-ECD

Liquid Chromatography

Liquid

• Mobile phase is liquid

• Packed chromatographic column

• More expensive than GC'

• No limitation with the properties of analyte

Mass Spectrometry Analysis

Measures an analyte that has been converted into an ion in the gas phase

GCMS and LCMS what’s different

it is converted into an ion during its gas phase

Electron Ionization

analytes are exposed to beams and loses a electron

Positive chemical ionization

soft ionization technique that produces less fragmentation in the mass spec.

Derivatization increases?

the number and spectrum complexity