Transcript Paul Cary EtG LADCP 2=06

Ethyl Glucuronide (EtG) –
New Strategy for Monitoring
Alcohol Abstinence
By: Paul L. Cary
Toxicology Laboratory
University of Missouri
EtG Discussion Points
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current approaches to alcohol monitoring
what is ethyl glucuronide
using EtG testing in abstinence monitoring
interpreting EtG testing results
establishing an appropriate EtG cutoff
EtG questions
client case reports
effective use of EtG testing for alcohol monitoring
Current alcohol testing approaches
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screening tests specific for ethanol, ethyl alcohol
urine, saliva or breath
positive results indicate presence alcohol
alcohol is rapidly cleared from the body
negative results don’t necessarily document abstinence
detection time = hours
alternative approaches alcohol can be measured
transdermally - SCRAM, WristAS
Problems Associated with Monitoring
Clients for Alcohol
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short detection window (hours)
current specimens:
 blood
(invasive)
 urine (tampering issues)
 breath/saliva (for best results requires onsite field visits)
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urine - fermentation
Alcohol is the most commonly
abused substance by drug court
clients and the most difficult
substance to detect in abstinence
monitoring.
Characteristics of a Good Alcohol Test:
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scientifically valid
therapeutically beneficial
legally defensible
direct measure of recent alcohol use
(specificity)
detection window of several days
(sensitivity)
Ethyl Glucuronide
COOH
O
OH
O
OH
OH
Et
What is ethyl glucuronide?
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direct metabolite of alcohol
purposed as a breakdown product in 1902
isolated in 1952
less than 0.02% of an ethanol dose is recovered as ethyl
glucuronide
unique biological marker
can be detected in various body fluids, hair and autopsy
samples
non-volatile, water-soluble, and stable in stored
specimens
Facts About Ethyl Glucuronide
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until recently no EtG testing commercially
available
a few hours after beginning of alcohol
consumption, EtG can be detected in urine and is
detectable up to 5 days after the complete
elimination of alcohol from the body
so far in > 15,000 serum and urine samples
determined by different groups, no false
positives have been reported using the
recommended testing method
Ethyl alcohol
Ethyl glucuronide
Time (days)
Testing for Ethyl Glucuronide
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not available as an “on-site” test - laboratorybased testing only
scarcity of testing options
recommended analysis LC/MS/MS (liquid
chromatography/ tandem mass spectroscopy)
testing is highly specific/very sensitive
results/cutoffs in ng/mL
Advantages of Ethyl Glucuronide
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unique biological marker of alcohol use (no false
positives)
direct marker indicating recent use
longer detection window (up to 5 days)
stable in stored specimens (non-volatile)
is not formed by fermentation
is not detected in the urine of abstinent subjects
may reduce “in the field” BAC testing by staff
Disadvantages of Ethyl Glucuronide
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testing available at very few laboratories
uses highly sophisticated technology (LC/MS/MS)
testing rather costly ($25.00 - $90.00)
detection window decreases as cutoff level is increased
casual, inadvertent, environmental alcohol exposure
could result in positive results
EtG production is variably between subjects
Interpretation of EtG Results in
Urine
Concentration Range of Urine EtG
Testing
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using LC/MS/MS
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linear range = 50 - 10,000 ng/mL
Urine EtG Concentrations Following
Alcohol Consumption:
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one 3.2% beer
> 3800 ng/mL @ 4 hours
detection up to 24 hours
(alcohol - 90 minutes)
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three 3.2% beers
detection up to 48 hours
(alcohol - 3.5 hours)
Urine EtG Concentrations Following
“Incidental” Alcohol Exposure:
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0.5 teaspoon of
communion wine
75 ng/mL @ 9 hours
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Purell hand
sanitizer
> 40 ng/mL @ 3 hours
Other Consumer Products that Pose
Incidental Exposure Concerns:
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over the counter medications (Nyquil)
mouthwashes (Listermint)
tincture of gingko biloba (herbal - memory)
foods containing alcohol (such as vanilla extract,
baked Alaska, cherries jubilee, etc.)
“non-alcoholic” beers (O’Doul’s)
AVERAGE ALCOHOL AND CALORIE CONTENT OF
REGULAR, LIGHT, AND NON-ALCOHOLIC BEER
Product
No.
% Alcohol
Calories
samples
per 100 ml
-----------------------------------------------------------------------------------------------------------Regular
163
5.0 [2.0-9.5]
43 [26-83]
Light
26
4.1 [2.4-5.4]
32 [19-43]
Nonalcoholic
13
0.3 [0.1-0.7]
17 [13-30]
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Alcohol in Food - Cook’s Illustrated Study
(2005) “A Few Sobering Thoughts”
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beef burgundy - three hours in oven, lid on, 40%
alcohol retained
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flambé recipes - igniting brandy over high heat
29% alcohol retained - igniting brandy in cold pan
57% alcohol retained
As a result of “incidental” exposure issues,
if ethyl glucuronide testing is to be used in
drug court client alcohol abstinence
monitoring, it is important to delineate in
client agreements/ contracts those products
that are expressly prohibited.
term - “innocent positive”; no alcoholic
beverage use - truly accidental
Establishing an Appropriate EtG Cutoff:
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detection time is significantly impacted by amount of
alcohol consumed
as the cutoff concentration of the EtG test is increased,
the detection window (length of time EtG will be
detected in urine) decreases
when monitoring for abstinence, interpretation of low
EtG levels is critical
similar to “passive” inhalation or poppy seed issues
@ 500 ng/mL =
8 hours detection
@ 250 ng/mL =
16 hours detection
@ 100 ng/mL =
25 hours detection
20 “Detox” Patients:
all subjects + @ 2.5 days
only one subject excluded
@ 3 days
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
only three subjects
excluded @ 4 days
500 ng/mL cutoff
250 ng/mL cutoff
17 still positive for EtG @ 4
days
What EtG cutoff to use?
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100 ng/mL cutoff - most sensitivity, longest detection period
(up to 5 days), for programs with strong client supervision, solid
treatment support, need to establish absolute alcohol prohibition
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250 ng/mL cutoff - balance between reasonable detection
window and exclusion of “incidental” exposure, detection period 2-3
days, for programs monitoring abstinence
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500 ng/mL cutoff - most conservative, shortest detection period
(1-2 days), for programs without detailed client contracts; limited client
tracking; without access to toxicology/clinical expertise or who want to
avoid risk
Positive EtG Result:
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any result reported as positive (using LC/MS/MS)
in excess of either the 250 or 500 ng/mL cutoff is
consistent with the recent use of alcohol-containing
products by a monitored client
studies examining “incidental” exposure using
huge amounts of mouthwash yielded EtG results <
300 ng/mL & alcohol-based hand disinfectants <
100 ng/mL
Ethyl Glucuronide Questions
Can alcohol based hand sanitizers result in
positive EtG results?
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YES!
Purrell Gel is 70% ethyl alcohol
anti-bacterial effect primarily due to alcohol
dermal absorption of alcohol well-documented
studies indicate urine EtG levels as high as 50
ng/ml with total detection time approximately 90
minutes
Does hot weather cause EtG to breakdown
during shipment?
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NO!
experiments in heating samples to the boiling point
demonstrates no breakdown of EtG
nitrites and blood in urine can cause EtG
deterioration
Are EtG results reliable enough for
client sanctioning purposes?
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YES!
using LC/MS/MS technology
EtG is highly specific for alcohol use
direct metabolite only present following recent
alcohol consumption
Are there any medications that could
produce a positive EtG result?
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YES!
while no false-positive tests for EtG reported
only ethyl alcohol produces EtG
many liquid medications (& gel-cap) include ethanol
as a solvent (cough syrup, etc.)
medications containing ethanol will result in low levels
of EtG (100 ng/mL)
Case Reports
Dilute Urine Case:
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client with a negative drug screen & negative
urine alcohol but dilute sample - creatinine =
11 mg/dL; behavioral indicators mixed; urine
EtG ordered and returned with a result of 5300
ng/mL; client subsequently admitted drinking
on weekends
Missed Screen Post New Year’s Eve:
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client missed a random January 2nd drug test;
on January 12th a standard urine screen was
negative for alcohol and other drugs; sample
analyzed for EtG with results indicating >
10,000 ng/mL; client admitted partying on
New Year’s Eve and having a “few” drinks
Poor Compliance - Communion Wine
Excuse:
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client with multiple relapses tests positive for
EtG at 860 ng/mL; when confronted, claims
communion wine consumption several times
per week; referred for increased treatment;
within a month arrested for drunkenness and
admits to several months of clandestine
alcohol use
Positive Urine Alcohol/Alcohol Use
Denied:
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a client’s routine urine drug test returns
positive for alcohol; client denies use; all
behavioral indicators positive; urine EtG
performed and results are negative;
determined urine alcohol presence due to
fermentation post collection.
Effective Use of EtG Testing
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too costly for widespread use in all drug
court clients
verify positive urine alcohol results; rule out
false positive urine alcohol (in vitro
fermentation)
surprise testing for suspicion of relapse
selective random testing in high risk
individuals
evaluating dilute urines
Final Thoughts:
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EtG testing more effectively detects
clandestine alcohol use in recovering clients
EtG testing added to monitoring panels may
enhance deterrent effect and discourage
alcohol relapse
surreptitious alcohol use by clients likely
more common than previously thought
Psychiatric Hospital Study (2002)
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35 forensic psychiatric inpatients -12 months (alcohol
related crimes)
samples collected following reentry/ resocialization
visits
146 urine samples collected, 14 tested positive for EtG
in all 14 cases, patients reported alcohol consumption
of alcohol equivalent to 3 - 15 standard drinks in the
12 - 60 hours prior to sample collection
Health Professionals Study (2003)
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100 sequential urines from health
professionals under contract for abstinence
monitoring
all samples tested negative for drugs and
alcohol
7 were positive for EtG
8 out 8 positive for EtG in “for cause” testing
www.ethylglucuronide.com
Laboratory Recommendations
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use a facility employing LC/MS/MS
establish a reasonable EtG cutoff (500
ng/mL)
carefully evaluate laboratories using EtG
“screening” tests
evaluate lab’s testing track record
Summary of Ethyl Glucuronide (EtG)
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EtG is a reliable bio-marker for recent alcohol usage
EtG remains detectable for up to five days
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two days - single drink
five days - heavy drinking
diagnostically & therapeutically useful
 enhanced deterrent
 more definitive relapse indicator
more costly than alcohol testing
available only from select laboratories
becoming increasingly popular testing approach for
determining continued abstinence
Ethyl Glucuronide
COOH
O
OH
O
OH
OH
Et