Ethyl Glucuronide (EtG)

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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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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

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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 dont necessarily document
  abstinence
• detection time hours
• alternative approaches alcohol can be measured
  transdermally - SCRAM, WristAS

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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

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

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Ethyl Glucuronide
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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

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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 gt 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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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

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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

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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

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Interpretation of EtG Results in Urine
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Concentration Range of Urine EtG Testing

• using LC/MS/MS
• linear range 50 - 10,000 ng/mL

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Urine EtG Concentrations Following Alcohol
Consumption

• one 3.2 beer gt 3800 ng/mL _at_ 4 hours
  detection up to 24 hours (alcohol - 90
  minutes)
• three 3.2 beers detection up to 48 hours
  (alcohol - 3.5 hours)

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Urine EtG Concentrations Following Incidental
Alcohol Exposure

• 0.5 teaspoon of 75 ng/mL _at_ 9 hours communion
  wine
• Purell hand gt 40 ng/mL _at_ 3 hours sanitizer

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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 (ODouls)

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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
Non- 13 0.3 0.1-0.7
17 13-30 alcoholic -------------------
--------------------------------------------------
---------------------------------------
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Alcohol in Food - Cooks 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

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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
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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

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_at_ 500 ng/mL 8 hours detection _at_ 250 ng/mL
16 hours detection _at_ 100 ng/mL 25 hours
detection
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20 Detox Patients
all subjects _at_ 2.5 days only one subject
excluded _at_ 3 days only three subjects excluded _at_
4 days 17 still positive for EtG _at_ 4 days
500 ng/mL cutoff
250 ng/mL cutoff
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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

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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 lt
  300 ng/mL alcohol-based hand disinfectants lt
  100 ng/mL

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Ethyl Glucuronide Questions
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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

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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

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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

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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)

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Case Reports
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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

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Missed Screen Post New Years 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 gt 10,000 ng/mL
  client admitted partying on New Years Eve and
  having a few drinks

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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

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Positive Urine Alcohol/Alcohol Use Denied

• a clients 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.

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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

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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

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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

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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

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www.ethylglucuronide.com
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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 labs testing track record

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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

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Ethyl Glucuronide