Ethyl Glucuronide (EtG) – New Strategy for Monitoring Alcohol Abstinence

By: Paul L. Cary Toxicology Laboratory University of Missouri

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

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

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

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:    scientifically valid therapeutically beneficial legally defensible   direct measure of recent alcohol use (specificity) detection window of several days (sensitivity)

Ethyl Glucuronide

COOH OH OH OH O O Et

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

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

Ethyl alcohol Ethyl glucuronide Time (days)

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

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

Disadvantages of Ethyl Glucuronide       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  using LC/MS/MS  linear range = 50 - 10,000 ng/mL

Urine EtG Concentrations Following Alcohol Consumption:  one 3.2% beer  three 3.2% beers > 3800 ng/mL @ 4 hours detection up to 24 hours

(alcohol - 90 minutes)

detection up to 48 hours

(alcohol - 3.5 hours)

Urine EtG Concentrations Following “Incidental” Alcohol Exposure:  0.5 teaspoon of communion wine  Purell hand sanitizer 75 ng/mL @ 9 hours > 40 ng/mL @ 3 hours

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)

AVERAGE ALCOHOL AND CALORIE CONTENT OF REGULAR, LIGHT, AND NON-ALCOHOLIC BEER Product No. samples % Alcohol Calories per 100 ml ----------------------------------------------------------------------------------------------------------- Regular 163 Light 26 5.0 [2.0-9.5] 4.1 [2.4-5.4] 43 [26-83] 32 [19-43] Non alcoholic 13

0.3 [0.1-0.7]

17 [13-30] ------------------------------------------------------------------------------------------------------------

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

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:     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: QuickTime™ and a Photo - JPEG decompressor are needed to see this picture.

all subjects + @ 2.5 days only one subject excluded @ 3 days 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?

   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 (1-2 days), for programs without detailed client contracts; limited client tracking; without access to toxicology/clinical expertise or who want to avoid risk most conservative, shortest detection period

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

Ethyl Glucuronide Questions

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

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

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

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)

Case Reports

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

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

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

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.

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

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

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 3 - 15 standard drinks in the 12 - 60 hours prior to sample collection

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

www.ethylglucuronide.com

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

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

Ethyl Glucuronide

COOH OH OH OH O O Et