Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

7BBFM127: The Chemistry of Drugs and Explosives > Alternative Biological Matrices > Flashcards

Alternative Biological Matrices Flashcards

You may prefer our related Brainscape-certified flashcards:
Periodic Table flashcards Chemistry 101 flashcards AP® Chemistry flashcards Organic Chemistry 101 flashcards
1
Q

LO

A

*** To understand the different matrices available for drug testing in toxicology
* To explain the application of novel biological matrices
* To discuss the advantages and disadvantages of hair, oral fluid and sweat for drug testing
**

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where are drug tests commonly done?

A

o Clinical settings
o Coroners’ investigations
o Forensic detection of crime
o Employment screening
o Therapeutic drug monitoring
o Sport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the different matrices that are available?

A

Endogenous fluids
Excretion
Secretions
Other examples

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are some endogenous fluids?

A

o Blood
o Cerebral spinal fluid
o Interstitial

When blood is not reliable anymore then CSF or interstitial fluids may be used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are some excretory matrices?

A

o Urine
o Faeces
o Breath e.g., breathalyser when driving

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are examples of secretions?

A

o Saliva (oral fluid)
o Tears
o Sweat
o Nasal mucus
o Breast milk
o Semen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are other examples of matrices which can be used?

A

o Gastric contents
o Tissues
o Hair
o Nails
o Teeth
o Vitreous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the two most commonly used matrices?

A

Urine and blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Tell me about Urine why is it a common matrix to use?

A
  • Most used matrix
  • High drug/ metabolite concentration
  • Available in large quantities
  • Show window of detection 1-3 days
  • Easy to adulterate/ substitute
  • Invasive collection
  • On-site testing available (point-of-case tests)
    o Get a qualitative outcome and then a positive outcome based on that which can then go on to further testing to get result from GC for example
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why is blood a commonly used matrix?

A
  • Detects drugs during biological activity –> pharmacokinetics
  • Low drug/ metabolite concentrations and small window of detection
  • Very short half-life (sometimes only a few hours)
  • Invasive collection –> trained staff required –> expensive
  • Possible risk of infection during collection/ analysis through needle used
  • On-site testing not possible –> standardised techniques availabl
  • Has to be stored at -20˚c which adds to cost
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

When is hair used as a matrix?

A

o Criminal investigations
o Family proceedings
o Drug treatment/ workplace drug testing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Whats the window of detection like for drugs with hair?

A

Long window of detection unless cut hair then removing evidence so if have long hair then long window

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What levels are required for hair analysis?

A

Low cut-off levels required –> trace concentrations
o All relative to how good equipment and method is

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is hair composed of?

A

o 65-95% proteins –> keratin
o 1-9% –> lipids
o Up to 5% pigments –> melanin and trace elements e.g., polysaccharides and water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the growth rate of hair?

A

roughly 0.35mm per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

A typical hair follicle

A

Supplied by blood to help with growth via follicle papilla which is how drugs can get into the hair

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How is the drug incorporated into hair?

A
  1. Blood (primary route)
  2. Sweat
  3. Environment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do drugs get into the hair via blood?

A

o During hair formation
o Passive diffusion from blood supplying the hair follicle
o Favouring un-ionised form of the drug/metabolite
o Drug binds to components in the matrix and to pigments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do drugs get into the hair via sweat?

A

o After hair formation
o Glands present near the route of the hair (sebum) –> sebum coats the hair shaft emerging from the follicle at the skin surface
o Secondary route is via touching hair and depositing sweat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How do drugs get into the hair via the environment?

A

o After hair formation
o Very little known about this route
o E.g., vaporisation of drugs leading to absorption  passive contamination due to high surface-to-volume ratio (this is unknown but a potential theory)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the steps to a hair collection procedure?

A
  1. Collect form the posterior vertex of the head
  2. Collect a lock of hair about the thickness of a pencil
  3. Cut as close to the scalp as possible
  4. Keeping route ends evenly aligned place hair in foil
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the stages of hair analysis?

A
  1. Divide hair into required sections
  2. Weigh individual sections
  3. Cut up finely or pulverise in a mill
  4. Apply wash regime for decontamination (removes any potential false positives from sweat e.g.,)
  5. Extract with acid/base or enzyme digestion
  6. Prepared for immunoassay analysis (get qualitative outcome)
  7. Confirm drug positive by GC-MS/LC-MS (get quantitative result)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the applications of hair analysis?

A
  • Provides a retrospective look at drug use:
    o Drug-facilitated sexual assaults
    o Drug history
    o Gestational drug exposure
    o Drug treatment programmes
    o Pre-employment testing
    o Post-mortem
  • Sectional analysis of hair strands can provide information on patterns of drug use
  • Testing not affected by short term abstinence or adulteration (this would have to be confirmed via urine)
  • All matrices have different uses for analysis and has to be considered which one is more appropriate for the situation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are some expanding applications for hair analysis?

A
  • Evaluating requests for driving license revoked previously for drug abuse
  • Evaluating claims that seized drugs are for personal use by demonstrating long-term habits
  • Monitoring out-of-competition use of anabolic steroids in athletes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the advantages of hair as a matrix?

A

o Provides a longer window of detection
o Detect changes over time
o Observed and non-invasive sampling (some may argue it is invasive)
o Ease of obtaining, storing, and transporting specimens
o Second specimen can be obtained

26
Q

What are the disadvantages of hair as a matrix?

A

o Inability to detect recent drug use
o Incomplete removal of external contamination by washing procedures- false positives
o Deposition of drug in hair reported to be dependent on hair colour
o Requires sensitive immunoassay and MS technology –> low concentrations present
o Dose concentration relationship unknown

27
Q

What are some other considerations with hair analysis?

A
  • Hair colour
  • Ethnic type
  • Cosmetic treatments
  • External conditions
28
Q

Research questions relating to hair

A
  • What are the mechanisms for incorporation of drugs into hair?
  • What is the relationship between dose and concentration of drugs in hair?
  • How is drug incorporation and retention in hair biased by race, sex, age, etc?
  • To what extent is externally applied drug (e.g., from sweat, sebum and environment) retained in hair?
29
Q

What is oral fluid?

A

saliva secreted in oral gland and oral fluid refers to things from mouth like saliva and food that’s been eaten recently for e.g.,)

30
Q

Oral fluid is a colourless fluid secreted into the oral cavity by what 3 glands?

A

o Parotid
o Submaxillary
o Sublingual

31
Q

What does oral fluid contain?

A

o 99% water
o 0.3% protein
o 0.3% mucin and cellular debris, blood etc.

32
Q

On average, how much saliva is produced a day?

A

500-1500 mL/day saliva produced

33
Q

Tell me about unstimulated saliva and stimulated saliva?

A
  • Unstimulated saliva pH: 5.6 to 7- the person is not given anything to produce more saliva such as citric acid. So, the unstimulated saliva is just normal saliva production.

If citric acid is given, the pH can rise to 8 which will change the drug concentration as the passive diffusion process is affected so have to be aware of this
When simulation took place, a study found that lower levels of cocaine were found due to the passive diffusion processes being effected

34
Q

Can saliva be used for point-of-care testing?

A

Yes

35
Q

How do drugs enter the blood?

A

via passive diffusion

36
Q

The degree of diffusion of the blood is influenced by what?

A

**o Pka of drug/ metabolite
o pH of saliva/ plasma **

If ionised the drug is trapped in saliva and cannot diffuse back to blood

  • Parent drug dominant over metabolite (parent have higher pKa than metabolite)- usually parent drug which is affected
37
Q

Tell me about the similarities between the oral fluid concentration and blood/plasma concentration?

A

o Estimation from the pH of oral fluid and blood, the protein binding of the drug and its pKa
o Acidic drugs: Blood > OF the equilibrium favours blood, hence oral fluid concentrations are less than for blood,
o **Basic drugs: Blood < OF **

38
Q

How is oral fluid collected and what are the different techniques to do this?

A
  • Ten-minute observation period is required before specimen collection
  • Expectoration (spitting) –> produced limited sample volume (less than 1 mL)
  • Stimulated –> e.g., chewing Teflon tape, gum, placing citric acid on tongue, absorption on cotton rolls
  • Specially designed devices include:
    **o Salivette **
     Cotton roll which is placed into participant mouth
     Filter in tube which causes OF out of colon and into solution
    **o Intercept **
     Like quantisal
    **o Certus **
     Like salivette
    **o Quanitsal **
     Place wide end on participants tongue or side of cheek
     The blue marker at top appears when 1 ml of sample collected
     Then place in tube with buffer which causes diffusion of sample out of white tube which would then go on to be tested
39
Q

What are the applications for oral fluid testing?

A
  • Pre-employment, random and post-accident drug testing
  • Home testing kits available for drug and alcohol detection
  • Portable testing instruments available for on-site testing
40
Q

What are the advantages of oral fluid as a matrix?

A

o Useful in detection of recent drug use
o Ready accessibility for collection (patients for instance undergoing chemotherapy may suffer from condition called ‘dry mouth’ which limits saliva samples, but some stimulants can be used to help increase saliva production)
o Observed and non-invasive collection
o Results may be related to behaviour/ performance e.g., refusing to keep sample in for the 10 minutes which can lead to low sample collection
o Parent drug can be the target of the assay
o POCT available

41
Q

What are the disadvantages of oral fluid as a matrix?

A

o Short detection window however show recent drug use compared to hair
o Collection volume may be device dependent, and some may dilute the sample
o Sample may be viscous
o Subjects may suffer from ‘dry mouth’ (physiology of the person)
o Drug concentrations of OF < urine (except after recent drug use)
o Requires sensitive immunoassays for MS technology

42
Q

Tell me about the section 5A Road traffic act (the penalty, what is tested and how its done)

A

Section 5A Road traffic act (OF being used)

  • Implemented in March 2015 –> new offence of ‘driving or being in charge of a motor vehicle with concentration of specific controlled drug with specific limit’
  • Penalty is 12 months ban plus fine of up to £5000 and/or up to 6 months in prison
  • 16 drugs:
    o Prescription drugs –> Clonazepam, diazepam, flunitrazepam etc
    o Illicit drugs –> cocaine (plus BZE- BZE main metabolite of cocaine), cannabis, ketamine etc
  • At present only kits for cocaine and cannabis are available for roadside testing
  • Field impairment tests –> can be conducted if tests are negative and if failed a blood sample is taken (however limitation due to short window of detection with blood, so need to design a better test)
43
Q

What are some examples of roadsides tests which can be used?

A
44
Q

What is sweat? What the the types of sweat?

A
  • Sweat is 99% water
  • **Insensible **sweat:
    o Not visible and caused by diffusion through the skin
    o 300-700 mL/day
  • Sensible sweat:
    o Actively excreted during stress and exercise
    o 2-4 L/hr
45
Q

The average person has 2.6 million sweat glands and what are the glands?

A

o Eccrine sweat
o Sebaceous sweat
o Apocrine sweat

o Secreted from different glands and locations in the body
* Drugs are incorporated into sweat via passive diffusion

46
Q

Tell me about **Eccrine sweat glands **(primary gland when sweat testing)

A

o Found almost on the entire body surface
o Highest density on palmar surface and the forehead
o Odourless, colour aqueous solution of sodium-, potassium-, calcium-, magnesium-chloride with traces of amino acids, amines, and vitamins
o pH of 4.0 to 6.0

47
Q

Tell me about Apocrine sweat glands

A

o Located in shaft of a hair follicle close to sebaceous glands
o Controlled by cholinergic or adrenergic agents
o Odourless viscous, cloudy, yellow white liquid
o Rich in cholesterol, triglycerides, and fatty acids
o pH of 6.0-7.5

48
Q

Tell me about **Sebaceous glands **

A

o Associated with hair follicles and located everywhere except palmar surfaces
o 300 glands per cm2 counted on the hairy part of the head
o Viscous, yellow-white liquid sebum
o Consists of triglycerides and was esters
o Hair bulb contains both apocrine and sebum  sweat and sebum cannot be examined separately
o pH 4.0 to 6.0

49
Q

How is a sweat sample collected?

A
  • Bandages, pieces of cotton, gauze, or towel
  • Sweat patch (PharmCheck):
    o Adhesive patch
    o Patch is applied to upper arm or back
    o Can be work for up to 14 days
    o Absorbent pad is stored
  • Quanitsal can also be used for sweat
50
Q

What are some applications for sweat?

A
  • Provides a cumulative measure of drug use
  • Useful for monitoring individuals for drug rehabilitation
51
Q

What are the advantages of sweat as a matrix?

A

o Patches can monitor drug intake for a period of days to weeks –> cumulative
o Non-invasive specimen collection
o Collection device is relatively tamperproof and shows evidence if tampered with

52
Q

What are the disadvantages of sweat as a matrix?

A

o Large variation in sweat production which could alter drug concentration presence
o Specimen volume unknown
o Risk of accidental removal of patch
o Risk of contamination during application/ removal
o For workplace testing not practical to wear a patch for several days
o Limited expertise and knowledge and lots of unknowns for drug dose relationship for e.g.

53
Q

Latent fingerprints can be used to collect what type of matrix?
Why are they good?

A
  • A different way to collect sweat (eccrine glands)
    o Quick sample collection
    o Non-invasive
54
Q

What are the two types of samples that can be collected from LFPs and what is each?

A

o Natural LFPs- not as good as could contain drugs some a surface you have touched for example so therefore if positive then a groomed LFP sample is used

o Groomed LFPs- further prove drug use, pre-treatment using hand washing procedure so that following 10 mins supervised the neat eccrine sweat sample is collected which is then analysed using mass spec

55
Q

Different analytical techniques such as what have show that LFPs contain drugs and metabolites?

A

o LC-MS
o Antibodies coupled with nanoparticles (also shows ridge lines which proves the sample came from that individual so not risk of swapping out samples for example)
o Point-of-care test

56
Q

What do you have to be aware of when designing tests for drug testing?

A
  • Useful when designing test as for instance with a urine test for cocaine you would want to test for metabolite over parent sample due to how the concentrations vary
57
Q

What are the windows of detection for the matrices talked about?
What are some points to consider with this?

A
58
Q

The current techniques used for analysis

A
59
Q

What is point-of-case testing?

A

**Point of care testing (POCT) **
* Testing conducted in close proximity to patient/subject
* Immediate result
* Used to aid diagnosis of disease, guide therapy or detect poisons

60
Q

How the different types of monitoring influences the analyte looked for in different test samples

A
61
Q

Conclusion

A
  • Each matrix is suitable for a particular application in relation to its specific characteristics:
    o Hair –> workplace drug testing, driving licence re-granting, drug-use history
    o Oral fluid –> roadside drug testing
    o Sweat –> monitoring drug abstinence
  • Important factors to consider:
    o Drugs pharmacokinetics
    o Drugs PKas
    o Matrices PH

7BBFM127: The Chemistry of Drugs and Explosives (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions