1. By: Paul L. Cary Toxicology Laboratory University of Missouri
Ethyl Glucuronide (EtG) – New Strategy for Monitoring Alcohol Abstinence
By: Paul L. Cary
Toxicology Laboratory
University of Missouri

2. EtG Discussion Points 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

3. Current alcohol testing approaches
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

4. Problems Associated with Monitoring Clients for Alcohol
short detection window (hours)
current specimens:
blood (invasive)
urine (tampering issues)
breath/saliva (for best results requires on-site field visits)
urine - fermentation

5. Alcohol is the most commonly abused substance by drug court clients and the most difficult substance to detect in abstinence monitoring.

6. Characteristics of a Good Alcohol Test:
scientifically valid
therapeutically beneficial
legally defensible
direct measure of recent alcohol use (specificity)
detection window of several days (sensitivity)

7. Ethyl Glucuronide

8. What is ethyl glucuronide?
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

9. Facts About Ethyl Glucuronide
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

11. Testing for Ethyl Glucuronide
not available as an “on-site” test - laboratory-based 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

12. Advantages of Ethyl Glucuronide
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

13. Disadvantages of Ethyl Glucuronide
testing available at very few laboratories
uses highly sophisticated technology (LC/MS/MS)
testing rather costly ($ $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

14. Interpretation of EtG Results in Urine

15. Concentration Range of Urine EtG Testing
using LC/MS/MS
linear range = ,000 ng/mL

16. Urine EtG Concentrations Following Alcohol Consumption:
one 3.2% beer > hours detection up to 24 hours (alcohol - 90 minutes)
three 3.2% beers detection up to 48 hours (alcohol hours)

17. Urine EtG Concentrations Following “Incidental” Alcohol Exposure:
0.5 teaspoon of hours communion wine
Purell hand > 40 3 hours sanitizer

18. Other Consumer Products that Pose Incidental Exposure Concerns:
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)

19. AVERAGE ALCOHOL AND CALORIE CONTENT OF REGULAR, LIGHT, AND NON-ALCOHOLIC BEER
Product No % Alcohol Calories
samples per 100 ml
Regular [ ] [26-83]
Light [ ] [19-43]
Non [ ] [13-30]
alcoholic

20. Alcohol in Food - Cook’s Illustrated Study (2005) “A Few Sobering Thoughts”
beef burgundy - three hours in oven, lid on, 40% alcohol retained
flambé recipes - igniting brandy over high heat 29% alcohol retained - igniting brandy in cold pan 57% alcohol retained

21. 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

22. Establishing an Appropriate EtG Cutoff:
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

23. @ 500 ng/mL =
8 hours detection
@ 250 ng/mL =
16 hours detection
@ 100 ng/mL =
25 hours detection

24. 20 “Detox” Patients: all subjects + @ 2.5 days
only one subject 3 days
only three subjects 4 days
17 still positive for 4 days
500 ng/mL cutoff
250 ng/mL cutoff

25. What EtG cutoff to use?
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
250 ng/mL cutoff - balance between reasonable detection window and exclusion of “incidental” exposure, detection period 2-3 days, for programs monitoring abstinence
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

26. Positive EtG Result:
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

27. Ethyl Glucuronide Questions

28. Can alcohol based hand sanitizers result in positive EtG results?
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

29. Does hot weather cause EtG to breakdown during shipment?
NO!
experiments in heating samples to the boiling point demonstrates no breakdown of EtG
nitrites and blood in urine can cause EtG deterioration

30. Are EtG results reliable enough for client sanctioning purposes?
YES!
using LC/MS/MS technology
EtG is highly specific for alcohol use
direct metabolite only present following recent alcohol consumption

31. Are there any medications that could produce a positive EtG result?
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)

32. Case Reports

33. Dilute Urine Case:
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
The importance of witnessed collection (for urine monitoring) can not be over-emphasized. As indicated on the slide, urine collections which are not witnessed are of little or no assessment value because of the propensity of drug court participants not to provide a legitimate sample (denial; efforts to hide relapse). The definition of “witnessed collections” is direct line-of-sight observation – basically staring at a participants genitals. Difficult? - yes! Uncomfortable? - no doubt! Necessary? - absolutely critical. Put another way; if drug courts don’t directly observe urine collections, they should not waste their time and money on testing efforts! It’s THAT important!
The success of monitoring depends on a legitimate specimen for testing. The most likely guarantor that a legitimate specimen will be produced is with direct-observation collections. Remember, a drug court can employ the absolute best testing methods available, but that testing is worthless if the sample has been tampered with (by the participant) prior to the testing process.

34. Missed Screen Post New Year’s Eve:
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
The importance of witnessed collection (for urine monitoring) can not be over-emphasized. As indicated on the slide, urine collections which are not witnessed are of little or no assessment value because of the propensity of drug court participants not to provide a legitimate sample (denial; efforts to hide relapse). The definition of “witnessed collections” is direct line-of-sight observation – basically staring at a participants genitals. Difficult? - yes! Uncomfortable? - no doubt! Necessary? - absolutely critical. Put another way; if drug courts don’t directly observe urine collections, they should not waste their time and money on testing efforts! It’s THAT important!
The success of monitoring depends on a legitimate specimen for testing. The most likely guarantor that a legitimate specimen will be produced is with direct-observation collections. Remember, a drug court can employ the absolute best testing methods available, but that testing is worthless if the sample has been tampered with (by the participant) prior to the testing process.

35. Poor Compliance - Communion Wine Excuse:
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
The importance of witnessed collection (for urine monitoring) can not be over-emphasized. As indicated on the slide, urine collections which are not witnessed are of little or no assessment value because of the propensity of drug court participants not to provide a legitimate sample (denial; efforts to hide relapse). The definition of “witnessed collections” is direct line-of-sight observation – basically staring at a participants genitals. Difficult? - yes! Uncomfortable? - no doubt! Necessary? - absolutely critical. Put another way; if drug courts don’t directly observe urine collections, they should not waste their time and money on testing efforts! It’s THAT important!
The success of monitoring depends on a legitimate specimen for testing. The most likely guarantor that a legitimate specimen will be produced is with direct-observation collections. Remember, a drug court can employ the absolute best testing methods available, but that testing is worthless if the sample has been tampered with (by the participant) prior to the testing process.

36. Positive Urine Alcohol/Alcohol Use Denied:
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.
The importance of witnessed collection (for urine monitoring) can not be over-emphasized. As indicated on the slide, urine collections which are not witnessed are of little or no assessment value because of the propensity of drug court participants not to provide a legitimate sample (denial; efforts to hide relapse). The definition of “witnessed collections” is direct line-of-sight observation – basically staring at a participants genitals. Difficult? - yes! Uncomfortable? - no doubt! Necessary? - absolutely critical. Put another way; if drug courts don’t directly observe urine collections, they should not waste their time and money on testing efforts! It’s THAT important!
The success of monitoring depends on a legitimate specimen for testing. The most likely guarantor that a legitimate specimen will be produced is with direct-observation collections. Remember, a drug court can employ the absolute best testing methods available, but that testing is worthless if the sample has been tampered with (by the participant) prior to the testing process.

37. Effective Use of EtG Testing
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

38. Final Thoughts:
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

39. Psychiatric Hospital Study (2002)
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 standard drinks in the hours prior to sample collection

40. Health Professionals Study (2003)
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

42. Laboratory Recommendations
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

43. Summary of Ethyl Glucuronide (EtG)
EtG is a reliable bio-marker for recent alcohol usage
EtG remains detectable for up to five days
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

44. Ethyl Glucuronide