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

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Presentation on theme: "Ethyl Glucuronide (EtG) – New Strategy for Monitoring Alcohol Abstinence By: Paul L. Cary Toxicology Laboratory University of Missouri."— Presentation transcript:

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

2 EtG Discussion Points n current approaches to alcohol monitoring n what is ethyl glucuronide n using EtG testing in abstinence monitoring n interpreting EtG testing results n establishing an appropriate EtG cutoff n EtG questions n client case reports n effective use of EtG testing for alcohol monitoring

3 Current alcohol testing approaches n screening tests specific for ethanol, ethyl alcohol n urine, saliva or breath n positive results indicate presence alcohol n alcohol is rapidly cleared from the body n negative results don’t necessarily document abstinence n detection time = hours n alternative approaches alcohol can be measured transdermally - SCRAM, WristAS

4 Problems Associated with Monitoring Clients for Alcohol n short detection window (hours) n current specimens: u blood (invasive) u urine (tampering issues) u breath/saliva (for best results requires on- site field visits) n 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: n scientifically valid n therapeutically beneficial n legally defensible n direct measure of recent alcohol use (specificity) n detection window of several days (sensitivity)

7 Ethyl Glucuronide

8 What is ethyl glucuronide? n direct metabolite of alcohol n purposed as a breakdown product in 1902 n isolated in 1952 n less than 0.02% of an ethanol dose is recovered as ethyl glucuronide n unique biological marker n can be detected in various body fluids, hair and autopsy samples n non-volatile, water-soluble, and stable in stored specimens

9 Facts About Ethyl Glucuronide n until recently no EtG testing commercially available n 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 n so far in > 15,000 serum and urine samples determined by different groups, no false positives have been reported using the recommended testing method

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11 Testing for Ethyl Glucuronide n not available as an “on-site” test - laboratory- based testing only n scarcity of testing options n recommended analysis LC/MS/MS n recommended analysis LC/MS/MS (liquid chromatography/ tandem mass spectroscopy) n n testing is highly specific/very sensitive n n results/cutoffs in ng/mL

12 Advantages of Ethyl Glucuronide n unique biological marker of alcohol use (no false positives) n direct marker indicating recent use n longer detection window (up to 5 days) n stable in stored specimens (non-volatile) n is not formed by fermentation n is not detected in the urine of abstinent subjects n may reduce “in the field” BAC testing by staff

13 Disadvantages of Ethyl Glucuronide n testing available at very few laboratories n uses highly sophisticated technology (LC/MS/MS) n testing rather costly ($ $90.00) n detection window decreases as cutoff level is increased n casual, inadvertent, environmental alcohol exposure could result in positive results n EtG production is variably between subjects

14 Interpretation of EtG Results in Urine

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

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

17 Urine EtG Concentrations Following “Incidental” Alcohol Exposure: n 0.5 teaspoon of75 9 hours communion wine n Purell hand> 40 3 hours sanitizer

18 Other Consumer Products that Pose Incidental Exposure Concerns: n over the counter medications (Nyquil) n mouthwashes (Listermint) n tincture of gingko biloba (herbal - memory) n foods containing alcohol (such as vanilla extract, baked Alaska, cherries jubilee, etc.) n “non-alcoholic” beers (O’Doul’s)

19 AVERAGE ALCOHOL AND CALORIE CONTENT OF REGULAR, LIGHT, AND NON-ALCOHOLIC BEER ProductNo. % AlcoholCalories samples per 100 ml Regular [ ] 43 [26-83] Light [ ] 32 [19-43] 0.3 [ ] Non [ ] 17 [13-30] alcoholic

20 Alcohol in Food - Cook’s Illustrated Study (2005) “A Few Sobering Thoughts” n beef burgundy - three hours in oven, lid on, 40% alcohol retained n flamb n 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: n detection time is significantly impacted by amount of alcohol consumed n as the cutoff concentration of the EtG test is increased, the detection window (length of time EtG will be detected in urine) decreases n when monitoring for abstinence, interpretation of low EtG levels is critical n similar to “passive” inhalation or poppy seed issues

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

24 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 20 “Detox” Patients:

25 What EtG cutoff to use? n 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 n 250 ng/mL cutoff - balance between reasonable detection window and exclusion of “incidental” exposure, detection period 2-3 days, for programs monitoring abstinence n 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: n 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 n 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? n YES! n Purrell Gel is 70% ethyl alcohol n anti-bacterial effect primarily due to alcohol n dermal absorption of alcohol well-documented n 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? n NO! n experiments in heating samples to the boiling point demonstrates no breakdown of EtG n nitrites and blood in urine can cause EtG deterioration

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

31 Are there any medications that could produce a positive EtG result? n YES! n while no false-positive tests for EtG reported n only ethyl alcohol produces EtG n many liquid medications (& gel-cap) include ethanol as a solvent (cough syrup, etc.) n medications containing ethanol will result in low levels of EtG (100 ng/mL)

32 Case Reports

33 Dilute Urine Case: n 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

34 Missed Screen Post New Year’s Eve: n 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

35 Poor Compliance - Communion Wine Excuse: n 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

36 Positive Urine Alcohol/Alcohol Use Denied: n 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.

37 Effective Use of EtG Testing n too costly for widespread use in all drug court clients n verify positive urine alcohol results; rule out false positive urine alcohol (in vitro fermentation) n surprise testing for suspicion of relapse n selective random testing in high risk individuals n evaluating dilute urines

38 Final Thoughts: n EtG testing more effectively detects clandestine alcohol use in recovering clients n EtG testing added to monitoring panels may enhance deterrent effect and discourage alcohol relapse n surreptitious alcohol use by clients likely more common than previously thought

39 Psychiatric Hospital Study (2002) n 35 forensic psychiatric inpatients -12 months (alcohol related crimes) n samples collected following reentry/ resocialization visits n 146 urine samples collected, 14 tested positive for EtG n 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) n 100 sequential urines from health professionals under contract for abstinence monitoring n all samples tested negative for drugs and alcohol n 7 were positive for EtG n 8 out 8 positive for EtG in “for cause” testing

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42 Laboratory Recommendations n use a facility employing LC/MS/MS n establish a reasonable EtG cutoff (500 ng/mL) n carefully evaluate laboratories using EtG “screening” tests n evaluate lab’s testing track record

43 Summary of Ethyl Glucuronide (EtG) n EtG is a reliable bio-marker for recent alcohol usage n EtG remains detectable for up to five days u two days - single drink five days - heavy drinking n diagnostically & therapeutically useful u enhanced deterrent u more definitive relapse indicator n more costly than alcohol testing n available only from select laboratories n becoming increasingly popular testing approach for determining continued abstinence

44 Ethyl Glucuronide


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