Download Detection of drug abuse and misuse using biological samples

References
1 Melanson, S.E., Baskin, L., Magnani, B., Kwong, T.C., Dizon, A., Wu, A.H. (2010). Interpretation
and utility of drug of abuse immunoassays: lessons from laboratory drug testing surveys.
Arch Pathol Lab Med 134, 735–739.
2 Becker, M.L., Kallewaard, M., Caspers, P.W., Visser, L.E., Leufkens, H.G., Stricker, B.H. (2007).
Hospitalisations and emergency department visits due to drug-drug interactions: a literature review.
­Pharmacoepidemiol Drug Saf 16, 641–651.
3 D’Onofrio, G., Becker, B., Woolard, R.H. (2006). The impact of alcohol, tobacco, and other drug use and
abuse in the emergency department. Emerg Med Clin North Am 24, 925–967.
4 Wu, A.H.B., McKay, C., Broussard, L.A., Hoffman, R.S., Kwong, T.C., Moyer, T.P., Otten, E.M., Welch, S.L.,
Wax, P. (2003). National Academy of Clinical Biochemistry laboratory medicine practice guidelines:
recommendations for the use of laboratory tests to support poisoned patients who present to the
­emergency department. Clin Chem 39, 357–379.
5 Okie, S. (2010). A flood of opioids, a rising tide of deaths. N Engl J Med 363, 1981–1985.
6 Kuehn, B.M. (2007). Opioid prescriptions soar: increase in legitimate use as well as abuse.
JAMA 297, 249–251.
7 US Department of Justice. National drug threat assessment 2011.
Available at: www.justice.gov/ndic/pubs44/44849/44849p.pdf [Accessed 1 May, 2012]
8 European Monitoring Centre for Drugs and Drug Addiction. Drug Profiles.
Available at: www.emcdda.europa.eu [Accessed 1 May, 2012]
9 Cone, E.J., Huestis, M.A. (2007). Interpretation of oral fluid tests for drugs of abuse.
Ann N Y Acad Sci 1098, 51–103.
10 Schepers, R.J., Oyler, J.M., Joseph, R.E. Jr., Cone, E.J., Moolchan, E.T., Huestis, M.A. (2003).
Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral
methamphetamine administration to human volunteers. Clin Chem 49, 121–132.
11 Krasowski, M.D., Pizon, A.F., Siam, M.G., Giannoutsos, S., Iyer, M., Ekins, S. (2009).
Using molecular similarity to highlight the challenges of routine immunoassay-based drug
of abuse/toxicology screening in emergency medicine. BMC Emerg Med 9, 5–22.
12 Crooks, C.R., Brown, S. (2010). Roche DAT immunoassay: sensitivity and specificity testing for
amphetamines, cocaine, and opiates in oral fluid. J Anal Toxicol 34, 103–109.
13 Montgomery, E. (2011). Trends in immunoassays for drugs-of-abuse testing. MLO Med Lab Obs 43, 17.
14 Porter, W.H. (2006). Clinical toxicology. In: Tietz textbook of clinical chemistry and molecular diagnostics
4th edition. Burtis, C.A., Ashwood, E.R., Bruns, D.E. eds. St. Louis, MO. Elsevier Saunders, 219–243.
15 Vearrier, D., Curtis, J.A., Greenberg M.I. (2010). Biological testing for drugs of abuse. EXS 100, 489–517.
16 Bosker, W.M., Huestis, M.A. (2009). Oral fluid testing for drugs of abuse. Clin Chem 55, 1910–1931.
17 Drummer, O.H. (2006). Drug testing in oral fluid. Clin Biochem Rev 27, 147–159.
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©2012 Roche
Roche Diagnostics International AG
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www.cobas.com
Drugs of abuse testing (DAT)
Detection of drug abuse and ­misuse using
­biological samples
cobas® modular platform
Flexible configurations for tailor made solutions
Introduction to DAT
With the cobas modular platform, the cobas 4000, 6000 analyzer series and cobas 8000 modular analyzer series, Roche has developed
a platform concept based on a common architecture that delivers tailor-made solutions for diverse workload and testing requirements.
The cobas modular platform is designed to reduce the complexity of laboratory operation and provide efficient and compatible solutions
for network cooperation.
“More than 1.7 million emergency department visits in 2006 were
Flexible and intelligent solutions
• Multiple configurations with tailor-made solutions for higher
efficiency and productivity
• Consolidation of clinical chemistry and immunochemistry with
more than 200 parameters for cost and workflow improvements
• Future sustainability through easy adaptation to changing
throughput and parameter needs
cobas 8000 modular analyzer series
Large volume
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<e 602>
<c 701>
cobas 6000 analyzer series
Mid volume
<c 501>
38 configurations
<c 702>
7 configurations
<e 601>
cobas 4000 analyzer series
Low volume
<c 311>
•C
onsistency of interaction with hardware, software and reagents
for less training and more staff flexibility
• Consistency of patient results due to a universal reagent
concept
<e 411>
3 configurations
associated with drug misuse or abuse, of which, 55 % involved an
illicit drug.”1
The use of diagnostic assays for “drugs of abuse” testing (DAT)
was originally introduced by criminal justice and law enforcement
agencies in order to detect illicit drug use. The scope of testing
has since expanded rapidly and led to a huge increase in the
number of drug tests performed in both therapeutic and legal/
forensic settings:
• Emergency room medicine
• Toxicology analysis
• Law court-mandated sobriety programs
• Penal and residential care rehabilitation programs
• Workplace safety programs
• Anti-doping monitoring in sport
• Crime scene investigations
Therapeutic application of DAT aims to improve patient safety
and treatment efficacy – a large proportion of patient visits to
the emergency department relate to the complications of drug
use.2-4 These visits can be the result of drug–drug interactions,
intentional or unintentional overdose of prescription or over-thecounter medications, or the use of illicit drugs. Data from the USA
show that the mortality rate from unintentional drug overdoses
has tripled in the last 15 years.5 For example, the 10-fold increase
in prescriptions for opiates observed since 1990 has been accompanied by a 10-fold increase in the number of deaths relating to
these drugs.5,6
Therapeutic DAT for a wide range of compounds has been introduced worldwide without significant controversy (see Figure 1
and subsequent section for description of the various classes of
drugs of abuse). The use of DAT for the screening of employees
in the workplace has, however, proved to be more controversial
and large-scale programs are predominantly limited to the USA,
where they were first introduced in the public sector during the
early 1980s. Private employers were subsequently encouraged to
join the “War on Drugs” and private sector screening programs
have since become widespread, especially within large companies
and corporations.
Major drug types identified by DAT
In 2007, the estimated cost of illicit drug use to American society totalled more
Roche DAT assays
than $193 billion, including direct and indirect costs relating to crime, health,
Amphetamine
•
and productivity.7
Barbiturates
•
Serum Barbiturates
•
Benzodiazepines
•
Serum Benzodiazepines
•
Cocaine
•
Methadone
•
Methadone Metabolite (EDDP)
•
Methaqualone
•
Opiates
•
Oxycodone
•
PCP
•
PPX
•
THC
•
LSD
•
Specimen Validity (Adulterants)
•
Psychostimulants
• Amphetamine
• Methamphetamine
• MDMA and derivatives
• Cocaine
• Ritalin
Drugs of abuse
testing (DAT)
Hallucinogens
• Cannabis
• Phencyclidine (PCP)
• Lysergic acid
­diethylamide (LSD)
Analgesics
• Opiates
(e.g. heroin, codeine)
• Non-opiate opioids (e.g.
fentanyl, methadone)
Anesthetics
(sedatives, hypnotics,
narcotics)
• Barbiturates
(e.g. pentobarbital)
• Benzodiazepines
(e.g. temazepam)
• Ketamine
• Alcohol
Figure 1: Types of drug commonly investigated by DAT
Available
Table 2: Roche DAT assay menu
(for urine samples unless otherwise indicated)
Psychostimulants
Amphetamine
Amphetamine is a stimulant of the central nervous system (CNS)
and increases the pharmacological activity of endogenous neurotransmitters, such as norepinephrine and dopamine. It is occasionally used therapeutically to treat narcolepsy and attention
deficit hyperactivity disorder. Because of its stimulating action,
the drug has a high potential for abuse and users are at considerable risk of developing tolerance and addiction. Amphetamine is
less potent than methamphetamine as it crosses the blood-brain
barrier to a lesser extent, but in uncontrolled situations the effects
are almost indistinguishable. Amphetamine is usually administered
by the oral or intravenous route and is metabolized to predominantly inactive metabolites by oxidative enzymes. The drug appears
rapidly in oral fluid following administration and parallels the
concentration found in plasma. Excretion of amphetamine via oral
fluid and urine is highly dependent on the pH of tissue fluid, which
can be influenced by the uptake of acids such as ascorbic acid.8,9
Amphetamine
EMIT
Enzyme multiplied immunoassay technique
Street names
Base, speed, whizz
RIA
Radioimmunoassay
Ingestion, insufflation, intravenous injection
EIA
Enzyme immunoassay
Method of
administration
LC-MS/MS
Liquid Chromatography tandem Mass spectrometry
Progressive effects
HPLC
High-performance liquid chromatography
GC-MS
Gas chromatography-mass spectrometry
“Rush” effect; increased confidence, sociability,
and energy, fatigue and appetite suppression,
restlessness, anxiety, depression, lethargy,
amphetamine psychosis
Table 1: Methods for detection of drugs
Half-life in plasma
Detection period in
urine (EIA):
Oral fluid (GC-MS):
7 – 24 hours
Methamphetamine and designer drugs
Methamphetamine is similar to amphetamine in terms of pharmacological effects and is the most widely abused, highly addictive
synthetic psychotropic drug.8 Methamphetamine can be easily
and cheaply manufactured in illicit laboratories and is abused
worldwide. The d-isomer is therapeutically used to treat attention
deficit hyperactivity disorder and for short-term treatment of obesity; it is considerably more potent than the l-isomer, which is sold
over-the-counter as a nasal decongestant. Methamphetamine is
metabolized to amphetamine by oxidative enzymes in the liver
following administration, but the parent drug remains detectable
in oral fluid where its concentration can be four-fold to that which
is present in plasma.8–10
In addition to methamphetamine, there are many chemically related
“designer drugs” being produced illicitly, including MDMA
(‘ecstasy’), MDEA (‘eve’), MDA, MBDB, and PMA/PMMA. These
are often produced as tablets that contain a mixture of drugs,
including synthetic cannabinoids and/or synthetic cathinones.
Most immunoassays for detecting methamphetamine show crossreactivity with MDMA, MDBD, and MDEA.
Methamphetamine
Street names
Crank, crystal meth, ice, meth, pervitin,
shabu, speed
Method of
administration
Ingestion, insufflation, intravenous injection,
smoked
Progressive effects
“Rush” effect; increased confidence, sociability
and energy, suppression of fatigue and appetite; restlessness, anxiety, depression, lethargy,
methamphetamine psychosis
Half-life in plasma
8 – 18 hours
Detection period in
urine (GC-MS):
Oral fluid (GC-MS):
22 – 96 hours
6 – 76 hours
Occasional use: 24 – 72 hours,
Chronic use: 9 days
20 – 50 hours
Enzyme immunoassay (EIA)
Gas chromatography-mass spectrometry (GC-MS)
Table 3: DAT profile of amphetamine9
Gas chromatography-mass spectrometry (GC-MS)
Table 4: DAT profile of methamphetamine9
Cocaine
Cocaine (chemical name: benzoylmethylecgonine) is a natural
compound extracted from the leaves of the coca plant and which
has only limited medical use as a topical anesthetic. Purified
cocaine has similar biological effects to amphetamine and has
been abused as a CNS stimulant since the early 20th century.8
Cocaine is rapidly metabolized and excreted by the kidneys and
so only small amounts of the parent drug are usually detectable in
urine. Immunoassays that detect cocaine therefore rely on antibodies raised against benzoylecgonine, which is one of the two
major cocaine metabolites in humans, and have a low sensitivity
for cocaine itself. Commercial immunoassays vary in their detection of other cocaine metabolites, which may lead to differing
results if samples are tested using more than one assay system.
Cocaine immunoassays generally show a low false-positive rate
due to the low structural similarity of benzoylecgonine with common medications or other illicit drugs.11
Cocaine
Street names
Charlie, coke, crack, snow, white
Method of
administration
Insufflation, intravenous injection, smoked
Progressive effects
Anesthesia, euphoria, confusion, depression,
convulsions, cardiotoxicity
Half-life in plasma
Detection period in
urine (benzoylec­
gonine, EIA):
Oral fluid (benzoylec­
gonine, GC-MS):
Cocaine: 1.4 – 1.8 hours;
benzoylecgonine: 5.4 – 7.6 hours
Occasional use: 14 – 59 hours;
Chronic use: 11 – 147 hours
Occasional use: >12 hours;
Chronic use: 36 – 72 hours
Analgesics
Opiates
Heroin (chemical name: diacetylmorphine) is a semi-synthetic
analgesic opioid used therapeutically for the treatment of severe
pain. The illicit form of the drug is usually smoked or solubilized
with a weak acid and injected, causing drowsiness, euphoria, and
a sense of detachment. Tolerance and physical dependence occur
following repeated use and cessation. In tolerant individuals leads
to characteristic withdrawal symptoms. Heroin is associated this
with far more accidental overdoses and fatal poisonings than any
other controlled substance.8
Heroin is difficult to detect in blood samples because it has a
plasma half-life of only 3 minutes; it is rapidly hydrolyzed to
6-monoacetylmorphine (6-AM) and then converted to morphine,
which is the main active metabolite. 6-AM is a metabolite unique
to heroin and can be detected in urine for 24 hours following
heroin use. Immunoassays currently marketed for detection of
opiate abuse use antibodies raised against morphine. This confers
a high sensitivity to structurally related opiates and opioids, such
as 6-AM, codeine, hydrocodone, and hydromorphone, but provides little cross-reactivity with oxycodone and its main metabolite oxymorphone. Dedicated oxycodone immunoassays with high
sensitivity to oxymorphone have been developed because this
drug is a frequently abused prescription medication and is now
prescribed in the USA more frequently than codeine, morphine,
and propoxyphene. Opiate immunoassays also do not cross-react
with synthetic opioids used for opioid maintenance treatment, such
as buprenorphine, as well as some commonly used opioid analgesics, such as fentanyl, meperidine (pethidine), and methadone.11
Table 5: DAT profile of cocaine9
Street names
Heroin: brown, H, horse, smack; other opiates
generally known by local generic or trade names,
e.g. codeine, morphine, OxyContin® and Eukodal®
(oxycodone), Vicodin® and Lortab® (hydrocodone)
Method of
administration
Ingestion, intramuscular or intravenous ­injection,
smoked
Progressive effects
Analgesia, sedation, euphoria, nausea, ­respiratory
inhibition, convulsions, coma
Half-life in plasma
Depends on type of opiate
Detection period
in urine:
Oral fluid (GC-MS):
Cannabinoids
Street names
Block, dope, ganja, grass, green, hash, pot,
skunk, weed
Method of
administration
Ingestion, smoked
Progressive effects
Euphoria; relief of anxiety, sedation, amnesia,
disorientation, paranoia
Half-life in plasma
5 – 6 days (THC-COOH)
Detection period in
urine (THC-COOH,
EMIT):
Oral fluids (THC, RIA):
Occasional use: 9 – 78 hours;
Chronic use: up to 67 days
2 – 24 hours
Occasional use: 7 – 54 hours (opiates, EMIT);
Chronic use: up to 11 – 12 days (total morphine, GC-MS)
Heroin: 2 – 24 hours, morphine: 2 – 12 hours
Enzyme multiplied immunoassay technique (EMIT)
Gas chromatography-mass spectrometry (GC-MS)
Table 6: DAT profile of opiate drugs9
Phencyclidine
Phencyclidine (PCP) was briefly used as a surgical anesthetic
but has since been removed from the market due to severe side
effects, such as convulsive seizures and hallucinations. Recreational use of PCP peaked in the USA during the 1960s and 1970s
and the drug was formally withdrawn in 1978. PCP is usually produced as either a liquid or a powder, but can also be produced in
tablet or spray form.
Phencyclidine
Street names
Angel dust, embalming fluid, PCP, rocket fuel
Method of
administration
Ingestion, insufflation, intravenous injection,
smoked
Progressive effects
Dissociative anesthesia, euphoria, altered
­perception, disorientation, agitation, combativeness, sedation, depression, psychosis, coma
Half-life in plasma
7 – 50 hours
Detection period in
urine (GC-MS):
Chronic use: up to 30 days
Gas chromatography-mass spectrometry (GC-MS)
Table 8: DAT profile of phencyclidine9
Enzyme multiplied immunoassay technique (EMIT)
Radioimmunoassay (RIA)
Opiates
Enzyme immunoassay (EIA)
Gas chromatography-mass spectrometry (GC-MS)
Hallucinogens
Cannabinoids
Cannabis (sometimes called marijuana) comprises the dried flowers and leaves of the plant cannabis sativum and is one of the
most widely consumed drugs throughout the world. Cannabis is
typically smoked, often mixed with tobacco, and long-term use
carries the same associated health risks as cigarette smoking.
The main psychoactive compound of cannabis is ∆9-tetrahydrocannabinol (THC), which can vary in concentration from 3 – 18 %.8
Screening of urine samples for cannabis is reliable and widely
used, although the detection of a positive sample does not provide exact information regarding impairment or the quantity or
frequency of use because THC can be deposited in fatty tissue
and released into the blood following activity and stress. The
inactive metabolite THC-COOH is most prominent in urine whereas THC can be detected in oral fluid because it is deposited in the
oral cavity when cannabis is smoked or ingested.
Table 7: DAT profile of cannabinoid drugs9
Anesthetics (hypnotics, sedatives, narcotics)
Barbiturates
Barbiturates are CNS depressants that produce effects ranging
from mild sedation to general anesthesia. The parent compound
barbituric acid was first synthesized in 1864 and the first pharmacologically active agent, barbital, was introduced in 1904. Only
about 50 of the 2,500 synthesized derivatives of barbituric acid
have ever been used medically. Due to their narrow therapeutic
range, the use of barbiturates as hypnotics/sedatives has largely
been superseded by benzodiazepines.
Benzodiazepines
Benzodiazepines are CNS depressants that induce a feeling of
calm and drowsiness, and are more commonly used than barbiturates due to their broader therapeutic range and lower risk of
dependence. Benzodiazepines are widely used to treat anxiety,
insomnia, and other psychological conditions, and represent a
broad family of compounds (clonazepam, diazepam, lorazepam,
oxazepam, and many more).
Barbiturates can be classified as ultra short-, short-, intermediate-,
or long-acting based on the duration of their sedative effect. Ultra
short-acting compounds, such as thiopental and methohexital,
are used for anesthesia, while long-acting compounds, such as
phenobarbital, are used in the treatment of epilepsy and other
types of convulsions.8
Benzodiazepine intoxication can be associated with behavioral
disinhibition, which can result in hostile or aggressive behavior.
The effect is most common when benzodiazepines are taken in
combination with alcohol, with combined use also increasing the
risk of a fatal overdose because both drugs act as CNS depressants. A similar fatal interaction can occur when benzodiazepines
are taken with opiates.8
Barbiturates
Benzodiazepines
Street names
Barbs, downers
Street names
Benzos, blues, nerve pills
Method of
administration
Ingestion, intramuscular or intravenous
injection
Method of
administration
Ingestion, intravenous or intramuscular
injection
Progressive effects
Sedation, lethargy, confusion, respiratory
­inhibition, coma
Progressive effects
Drowsiness; dizziness; muscle relaxation
Half-life in plasma
Depends on type of benzodiazepine;
diazepam: 21 – 37 hours
Half-life in plasma
Detection period in
urine (GC-MS):
Oral fluid (GC-MS):
Depends on type of barbiturate;
amobarbital: 20 hours
Depends on type of barbiturate;
amobarbital: 5 – 6 days
Depends on type of barbiturate;
amobarbital: 50 hours
Detection period in
urine (EMIT):
Oral fluid (GC-MS):
Depends on type of barbiturate;
diazepam: 2 – 7 days
Depends on type of barbiturate; diazepam:
<5 – 50 hours
Gas chromatography-mass spectrometry (GC-MS)
Enzyme multiplied immunoassay technique (EMIT)
Gas chromatography-mass spectrometry (GC-MS)
Table 9: DAT profile of barbiturate drugs9
Table 10: DAT profile of benzodiazepine drugs9
New and emerging drugs of abuse
Several new types of drug have recently become recognized as
drugs of abuse:
• Ketamine
• Synthetic cannabinoids
• Khat and synthetic cathinones
• Piperazines and derivatives
• Prescription painkillers
Ketamine is used as a sedative, analgesic, and anesthetic in
emergency medicine, as well as an anti-depressant in some
patient groups. The drug can be ingested, insufflated, or injected
and the effects are similar to PCP in producing a state of dissociative anesthesia and altered perception that lasts for several
hours.8
Synthetic cannabinoids, such as “Spice” in K2 products, are cannabinoid receptor agonists that mimic the effect of THC, although
little is known about their detailed pharmacology or toxicology.
Synthetic cannabinoids were first developed in the 1980s as
investigational drugs by official laboratories, such as the Hebrew
University Jerusalem (HU) or Sterling Winthrop (WIN). Some
substances are therefore classified according to their place of
development, such as HU-210 or WIN-48. Their effects are similar
to cannabis but individuals may additionally experience elevated
blood pressure and/or paranoia within minutes of use. Fatalities,
suicides, and cases of acute psychosis have been reported after
consumption of Spice in combination with alcohol and other drugs.
High sensitivity LC-MS/MS, GC-MS, and HPLC are currently the
state-of-the-art methods used for detection of synthetic cannabinoids, but the large number of clandestine laboratories producing
new substances and the lack of reference materials and deuterated internal standards make it difficult to establish standardized
testing methods.8
Khat comprises the leaves and fresh shoots of Catha edulis Forsk,
which are chewed in order to absorb the two principal active
components, cathinone and cathine. Both active components are
structurally related to amphetamine and induce similar effects,
although they are both less potent. Synthetic cathinones such
as mephedrone (also known as “bath salts” or “plant food”) are
derivatives of cathinone and are produced illicitly as powders or
tablets for ingestion. They are also occasionally found in combination with synthetic cannabinoids in samples of K2 products.8
Analytical methods for DAT
“The performance of the Roche DAT assays suggests these new
homogeneous screening assays will be an attractive alternative to
existing more labor-intensive enzyme immunoassays.”12
Routine DAT is usually a two-step process:
1. Initial batch-wise screening of samples
2. Confirmatory testing of all samples identified as positive
Immunoassays were first introduced in the 1970s and are currently the most widely used method for screening biological
samples for drugs of abuse.13,14 Immunoassays have become fully
automated in order to make DAT as efficient and cost-effective
as possible and modern assay platforms are capable of screening
hundreds of samples within a short space of time. The disadvantage of high-throughput immunoassays is that they typically only
screen for a single compound and can only provide qualitative or
semi-quantitative data.
Confirmatory testing of samples identified as positive by a
screening method is usually required for legal reasons. Reference methods, such as GC-MS and LC-MS/MS, are usually more
expensive and technically demanding than immunoassay-based
screening. However, results are quantitative and it is possible to
identify many different compounds within a single sample. Many
emergency departments only have access to confirmatory testing by referral of samples to an off-site reference laboratory and
therefore turnaround time is usually not fast enough to aid patient
management in real time.11
Biological samples for DAT
“While urine remains the most common body fluid used for testing
drugs of abuse, over the last several decades the use of alternative
matrices, such as blood, sweat, oral fluid, and hair has increased
dramatically.”15
Urine is most commonly used for DAT because it is easy to collect
in large volumes and does not require pre-analytical preparation.
Increasing automation and protocol homogenization have also
made urine analysis fast and cost-effective. Blood or serum is also
commonly used for DAT, although the taking of a sample requires
clinical training and there is a risk of infection even when sterilized equipment is used. The handling and processing of blood
and blood products also requires more stringent laboratory protocols compared with other sample types.
The main advantages offered by other sample types, such as oral
fluid and hair, are the non-invasiveness and simplicity of their
collection, which does not require medical staff or special restroom facilities with same-sex collectors. The lack of opportunity
for sample adulteration and a lower risk of infection are further
advantages. The higher content of parent drug within oral fluid
and blood may mean these types of sample are a superior indicator of recent drug use.16 However, the protein content of oral
fluid is low compared with blood samples and flow rate can vary
depending on the emotional and fed state of the individual.17
Obtaining samples from individuals with dry mouths can be difficult and requires longer collection times. Illicit drugs that reduce
oral fluid secretion include amphetamines and cannabis; commonly used drugs having the same effect include antihistamines,
antipsychotics, anticholinergics, and some antidepressants. Oral
fluid production can be stimulated by the use of agents such as
citric acid sweets and chewing gum, but this inevitably changes
the pH and concentration of drug in the oral fluid. A range of
­specialized collection devices has been developed in order to
support the collection of oral fluid samples for DAT. These devices
are designed to either preserve samples for safe transport to
conventional laboratory-based screening or are instead incorporated into a small testing device capable of providing rapid yes/
no determinations. These devices are ideally suited for oral fluid
testing used as part of “driving under the influence of drugs”
detection programs, criminal justice programs, and the monitoring
of medication compliance and workplace safety schemes.16
Diagnostic tests utilizing oral fluid or hair have not been in
development as long as urine- or blood-based assays and often
rely on non-homogeneous protocols that present challenges to
automation and potentially limit laboratory throughput. Perhaps
the greatest current limitation of the testing of new sample types,
however, is the lack of controlled drug administration studies to
inform the interpretation of results.
“The use of oral fluid has been found to offer significant promise
when detection of relatively recent drug use is sought in a noninvasive manner.”17
The future of DAT
The aim of achieving ever more accurate and reliable results
using the complementary methods of immunoassay and mass
spectrometry, combined with the expanding number of settings
in which DAT is being applied, is driving innovation in the field
of DAT. Analysis of blood, hair, urine, and oral fluid all present
­specific advantages and disadvantages depending on the question being asked and it is possible that DAT techniques may
diversify further rather than becoming consolidated into a single
method suitable for every scenario. Advances in diagnostic and
information technology, combined with increasingly stringent
legal and medical regulations, should ensure that DAT continues
to evolve for the maximum benefit of both patients and healthcare
providers.
References
1 Melanson, S.E., Baskin, L., Magnani, B., Kwong, T.C., Dizon, A., Wu, A.H. (2010). Interpretation
and utility of drug of abuse immunoassays: lessons from laboratory drug testing surveys.
Arch Pathol Lab Med 134, 735–739.
2 Becker, M.L., Kallewaard, M., Caspers, P.W., Visser, L.E., Leufkens, H.G., Stricker, B.H. (2007).
Hospitalisations and emergency department visits due to drug-drug interactions: a literature review.
­Pharmacoepidemiol Drug Saf 16, 641–651.
3 D’Onofrio, G., Becker, B., Woolard, R.H. (2006). The impact of alcohol, tobacco, and other drug use and
abuse in the emergency department. Emerg Med Clin North Am 24, 925–967.
4 Wu, A.H.B., McKay, C., Broussard, L.A., Hoffman, R.S., Kwong, T.C., Moyer, T.P., Otten, E.M., Welch, S.L.,
Wax, P. (2003). National Academy of Clinical Biochemistry laboratory medicine practice guidelines:
recommendations for the use of laboratory tests to support poisoned patients who present to the
­emergency department. Clin Chem 39, 357–379.
5 Okie, S. (2010). A flood of opioids, a rising tide of deaths. N Engl J Med 363, 1981–1985.
6 Kuehn, B.M. (2007). Opioid prescriptions soar: increase in legitimate use as well as abuse.
JAMA 297, 249–251.
7 US Department of Justice. National drug threat assessment 2011.
Available at: www.justice.gov/ndic/pubs44/44849/44849p.pdf [Accessed 1 May, 2012]
8 European Monitoring Centre for Drugs and Drug Addiction. Drug Profiles.
Available at: www.emcdda.europa.eu [Accessed 1 May, 2012]
9 Cone, E.J., Huestis, M.A. (2007). Interpretation of oral fluid tests for drugs of abuse.
Ann N Y Acad Sci 1098, 51–103.
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