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Urine Drug Screening
Dr. Patricia Mark
November 23, 2012
Basics
• Urine drug screening must always be discussed with
patients ahead of time. It is part of the physician/
patient agreement which all patients on MMP sign
• All patients must be treated the same way, and always
with respect
• UDS is not a means of punishing—rather, it is a tool to
help best management
Why?
• To ensure that prescribers can help and support MMP
patients to begin recovery and achieve stability
• Provides objective evidence of compliance with the
treatment plan
• Are patients taking medications as prescribed?
• Are patients using illicit substances?
• Adjust treatment plans if necessary to work towards best
outcomes for patients on opioids for opioid addiction or
chronic pain.
Why?
• UDS is only one of several ways in which physicians
can assess patients’ stability
• Careful history taking
• Frequent reassessment
• Contact with pharmacist
• Collateral information
Value of self-reporting of
noncompliance
• Can be significantly unreliable in patients suffering
from addiction disorders
• If UDS is found to be discordant with history of
medications:
• Review medical records
• Review PharmaNet
• Collateral information from significant others
How?
• Urine specimens produced at office visits before
physician encounter
• Supervised collection: bags, jackets, hoodies all left
outside bathroom. Patient given labelled specimen
container
• Urine temperature tested immediately
• Specific gravity checked if indicated
• Witnessed collection: seldom done, as an invasion of
patient privacy; may sometimes be necessary
How?
• Enzyme Immunoassay (EIA)
• Specific anti-drug antibody added to urine. If that drug is
present, antibody binds to drug giving a measurable
indicator reaction as “positive”
• MMP protocol uses methadone metabolite, opioid,
cocaine, benzo and methamphetamine screens
How?
• Gas chromatography
• Mass spectroscopy
•
GC separates and quantifies drug components.
•
MS specifically identifies them.
•
Gold standard of urine toxicology but expensive
•
Each test is about $40
When?
• Collected at every clinic visit — may not necessarily
be tested
• Random samples — collected at varying intervals
every 3 or 4 months and tested
• Random UDS is preferable and more valuable and
should be used for all patients with methadone carries
Which opioids show up in UDS?
Metabolites of:
• Heroin
• Morphine
• Codeine shows as morphine which is a metabolite of
codeine
• Reliably detected on regular EIA testing
Heroin
• Metabolizes to diacetyl morphine and then to 6-monoacetyl morphine (6-MAM)
• These metabolites easily detected in standard opioid
EIA testing from the 300 mg/mL level for up to 2 days
after a single IV or inhaled heroin dose
• 6-MAM metabolite is unique to heroin, exceptionally
useful forensic tool. Detectable only up to 12 hours
post-use, after which metabolizes to morphine
Morphine
• Presence of morphine in UDS can indicate use of
heroin, morphine, codeine or poppy seeds
• Urine from heroin users typically contains substantial
quantities of morphine and smaller quantities of
codeine reflecting poppy fluid contents
• Dividing morphine levels by codeine levels yields a
valuable ratio. Morphine: codeine ratio of more than
2:1 as determined by GCMS is corroborative evidence
of heroin use
Codeine
• Nearly identical to morphine in structure
• Easily detected by opioid EIA testing
• Metabolizes to morphine thus placing patients at risk
of being identified as abusing morphine
• Morphine: codeine ratio of less than 2:1 in codeine use
• Greater than 2:1 suggests morphine, heroin or poppy
seed use
Drugs of interest to methadone
prescribers: oxycodone
• Is a semi-synthetic opioid, shows up in only about
10% positive tests
• There is a specific EIA for oxycodone that is reliable
• Problems associated with oxycodone screening
include false negatives for patients for whom
oxycodone has been prescribed
Drugs of interest to methadone
prescribers: oxycodone
• Rapid metabolizers on oxycodone may also show
negative UDS as urine levels are too low
• GCMS may be necessary to confirm presence or
absence of oxycodone
Other synthetic opioids: fentanyl
• Wholly synthetic and does not react with EIA
morphine antibody. Needs either a specific EIA or
GCMS to confirm presence or absence.
• Patients who are on fentanyl and show positive for
opioids WHICH IS NOT POSSIBLE using standard
tests are abusing other opioids which react with the
standard EIA testing.
Methadone
• Is a wholly synthetic opioid which does not show up
on standard testing. Needs a specific EIA for
methadone metabolites which is virtually 100%
sensitive.
• All UDS kits, whether point-of-care testing or in labs,
use the specific EIA for methadone metabolites to
eliminate possibility of adulteration with methadone.
Hydromorphone
• Is a semi-synthetic opioid which may or may not show
up on routine UDS with standard opioid EIA testing
but more likely to show up if very high dosing
• Will require GCMS or specific EIA to confirm presence
or absence
Buprenorphine
• Is a semi-synthetic morphine-based molecule which
has been so altered that does not show up on
standard opioid EIA testing
• Specific and highly reliable EIA tests available in labs
and in point-of-care test kits
Other confounding variables
• Poppy seed from the opium poppy Papaver
Somniferum contains small amounts of morphine and
codeine
• Baked goods with poppy seeds are widely available
• Consumption of one poppy seed Danish streusel
pastry can easily produce positive opioid EIA tests
• Positive UDS can last for 24 hours
Poppy seeds
• Morphine:codeine ratio in poppy seed ingestion is
also 2:1 or greater, consistent with opium poppy fluid
as the opiate source of heroin and poppy seeds
• Difficult to determine whether opioid-positive EIA is
due to poppy seed or heroin use
• High levels of morphine more likely to be heroin but
may be misleading
• Advise patients to avoid baked goods with poppy
seeds
Fluoroquinolones
• Can also produce positive-opioid EIAs
• Is correlated to peak levels. In one study, urine
collected at 6–8 hours after fluoroquinolone ingestion
was 100% (false) positive for opioids
• Essentially unknown why fluoroquinolones have this
effect
• If a true false positive, GCMS will demonstrate no
opioid present
Benzodiazepines
• Always monitored by UDS, as are contraindicated for
patients on the MMP
• EIA for benzos is based on the diazepam antibody
• Shows reliably positive test for diazepam and
alprazolam
• Most diazepam EIAs do not detect clonazepam or
lorazepam
• GCMS is needed to identify both these benzos
Urine detection time frame
• Methadone
4–5 days
• Opioids
2–3 days
• Cocaine/metabolites 2–4 days
• Benzodiazepines
1–42 days
• THC single use
2–3 days
• THC habitual use
up to 12 weeks
• Methamphetamine
3–5 days
• Alcohol
6–24 hours
Other exceptions
• Z drugs – zopiclone and zaleplon are not detected in
spite of the fact that they metabolize down to benzos
• Chloral hydrate not detected—seldom now prescribed
except on occasions in hospital
Sertraline
• Patients on sertaline may produce intermittent false
positive benzo EIA specimens
• Due to a metabolite of sertraline
• Chemical structure of sertraline and its metabolite bear a
striking resemblance to diazepam which is the likely
cause of false positive reactions
• GCMS needed, if necessary, to determine the presence of
absence of specific benzos
UDS interpretation
• What shows in UDS is important
• What doesn’t show in UDS is equally important:
• Methadone metabolites
• Benzos
• Synthetic and semi-synthetic opioids
Limitations of UDS
• Assesses the presence or absence of a particular drug
and/or metabolite at a specific threshold of
concentration at a specific time
• Unexpected result does not diagnose
•
Abuse or addiction
•
Physical dependence
•
Diversion
• Does not provide accurate information on
•
Time of last use
•
Amount and frequency of use
Potential harms of UDS
• Incorrect interpretation of UDS could result in:
• Unwarranted discontinuation of opioids
• Damage to physician/patient relationship
• If very unexpected result, especially with POC testing,
always get laboratory confirmation
• Potential for false reassurance
• Adulteration/cheating
• Alteration of behaviour in anticipation of UDS, hence need
for random UDS
Consequences of “dirty” urine drug
screens
• Always review results of UDS with patient
• UDS result one of many factors taken into account
when making clinical decisions
• Review physician/patient agreement
• Review treatment plan
• Increase frequency of office visits
• Methadone dose if opioid-positive: is it appropriate?
• May have to discontinue carries in the face of
instability
• Increase counselling and other support services
Conclusion
• Urine drug screening is an important part of the
comprehensive care of patients who are on MMP or
are receiving opioids for chronic pain and must be
undertaken in a respectful, nonjudgmental manner
• Should be considered as an objective test within the
greater biopsychosocial context
• Should always be interpreted in the context of broad
based clinical care of the individual patient
Reference:
Tenore PL. Advanced urine toxicology testing. Journal of
Addictive Diseases. 2010 Oct; 29(4):436–48.
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