The roles of phosphatidylethanol, ethyl glucuronide, and ethyl sulfate in identifying alcohol consumption among participants in professionals health programs (2024)

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The roles of phosphatidylethanol, ethyl glucuronide, and ethyl sulfate in identifying alcohol consumption among participants in professionals health programs (1)

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Drug Test Anal. Author manuscript; available in PMC 2021 Aug 31.

Published in final edited form as:

Drug Test Anal. 2020 Aug; 12(8): 1102–1108.

Published online 2020 Jul 3. doi:10.1002/dta.2809

PMCID: PMC8406557

NIHMSID: NIHMS1734262

PMID: 32309913

Gary M. Reisfield,1 Scott A. Teitelbaum,1 Shannon O. Opie,2 Joseph Jones,3 Deborah G. Morrison,1 and Ben Lewis1

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The publisher's final edited version of this article is available at Drug Test Anal

Abstract

Direct alcohol biomarkers, including urinary ethyl glucuronide (EtG), urinary ethyl sulfate (EtS), and blood phosphatidylethanol (PEth), are used to monitor alcohol abstinence in individuals who are mandated to abstain.

In this consecutive case series study, we examined 1000 forensic reports of participants enrolled in a professionals health program who were contractually obligated to abstain from alcohol and who underwent recovery status evaluations. We identified 52 evaluations in which urinary EtG, EtS, and blood PEth were measured and which produced a positive result for at least one of these analytes.

PEth, at a cutoff concentration of 20 ng/mL, revealed alcohol use more frequently than EtG or EtS at our laboratory’s cutoff concentrations of 100 and 25 ng/mL, respectively. This was true, as well, at alternative EtG/EtS cutoff concentrations of 200/50, 300/75, and 400/100 ng/mL. PEth was more likely than EtG/EtS to be positive in participants previously diagnosed with alcohol use disorders (AUD), whereas EtG/EtS was more likely than PEth to be positive in participants without AUD.

In this study, blood PEth was the most sensitive biomarker for evidencing alcohol use.

Keywords: alcohol, alcohol use disorder, ethyl glucuronide, ethyl sulfate, phosphatidylethanol

1 |. INTRODUCTION

Some individuals are required to abstain from alcohol consumption. Self-reports are often unreliable in individuals with alcohol use disorder (AUD), who may underreport or fail to disclose their drinking.1,2 Thus, alcohol testing is an essential component of monitoring in these situations. Alcohol itself is measurable in blood, breath, and urine for only several hours after consumption, making it inadequate as a sole biomarker for abstinence monitoring. Consequently, abstinence typically is monitored through the measurement of other direct alcohol biomarkers in urine, blood, hair, or some combination of these matrices. Urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) are minor alcohol metabolites that have commonly been used for more than a decade as measures of abstinence. More recently, blood phosphatidylethanol (PEth) has gained acceptance in a variety of clinical and forensic contexts.38

Professionals health programs (PHPs) provide non-disciplinary monitoring and advocacy services for healthcare professionals with substance use disorders. Because these individuals are often promiscuous regarding their drug choices, PHP monitoring contracts for individuals with substance use disorders involving any drug class typically include injunctions against the use of all classes of drugs of potential abuse, including alcohol—regardless of whether they have a history of AUD.

PHP participants are sometimes required to undergo independent medical evaluations (IMEs) for a variety of reasons, including missed or failed drug tests, production of dilute urine specimens, driving under the influence of drugs or alcohol arrests, suspected impairment or other behavioral issues, and return-to-work after treatment. These IMEs comprise physician review of PHP referral documents, face-to-face evaluation of the participant, communications with collateral sources of information, and drug testing for pertinent drugs of potential abuse, including alcohol. Physicians then proffer diagnostic formulations and, if indicated, treatment recommendations.9,10

Most PHPs use EtG as the analyte of choice for detecting alcohol consumption.11 A consensus statement on drug testing by the American Society of Addiction Medicine concluded that PEth has promising clinical applications, while acknowledging that most of the expert panel members were not yet familiar with this biomarker.11 Indeed, a query of the U.S. National Library of Medicine, using its PubMed.gov search engine and employing the search strategy (phosphatidylethanol OR PEth) and filtered for human studies, returned 513 abstracts, only one of which was a study on the use of PEth in PHP participants. Skipper and colleagues reported that blood PEth, performed in series with urine EtG/EtS, had value in adjudicating cases in which participants produced low concentrations of these urinary metabolite(s) but initially denied consuming alcohol.12

The purpose of the present study was to compare the relative prevalence of blood PEth and urinary EtG and EtS among PHP participants who were contractually obligated to abstain.

2 |. MATERIALS AND METHODS

The University of Florida Institutional Review Board (IRB-01) approved the study in January 2017, and a retrospective chart review was conducted under a waiver of informed consent.

2.1 |. Chart review methods

One thousand consecutive reports were sampled from a database of recovery status IMEs conducted on PHP participants by faculty of the Division of Addiction Medicine, Department of Psychiatry, at the University of Florida College of Medicine. IMEs were performed between 1 January 2014 and 30 March 2017. Participants were permitted to schedule their IMEs up to 30 days in advance; thus they had advance notice of drug testing. None of the participants underwent alcohol use disorder treatment within 60 days before the IME. IMEs meeting the following criteria were included in the current investigation: IMEs included laboratory results for (a) urinary EtG, (b) urinary EtS, and (c) blood PEth, as well as (d) a positive result for at least one of the analytes.

The following data were collected from the included reports: (a) presence or absence of AUD, (b) presence or absence of alcohol-related referral for the IME, (c) gender; (d) urine EtG concentration, (e) urine EtS concentration, and (f) blood PEth concentration.

2.2 |. Data analysis

The primary analysis involved comparison of detection rates between EtG, EtS, and PEth. Of additional interest was whether the pattern of detection rates for these tests would vary by AUD history or involvement of alcohol in IME referral. To inform potential applications of analyte testing in varied contexts, we also describe results under several alternative EtG and EtS concentration cutoffs. Although the value of the current report relies more on descriptive statistics, t-tests, chi-square analyses, and Fisher’s Exact Test were used where appropriate. The latter was used most often, as cross-tab comparison of analyte detection necessarily included a cell with no representation (individuals negative for all analytes were excluded from study).

2.3 |. Analyte detection methods

Urine EtG/EtS and dried blood spot (DBS) PEth were analyzed at United States Drug Testing Laboratories (USDTL, Des Plaines, IL, USA). EtG and EtS were analyzed using a method based on previously published reports.13,14 Briefly, 50 μL of urine was diluted with 1000 μL of an aqueous internal standard solution that contained 50 ng/mL of EtG-d5 and ETS-d5. Separation was accomplished by injecting 7 μL of the prepared specimen on a Phenomenex Hyper-carb porous graphitic column (50 × 2.1 × 3 μm particle size) using 0.1% formic acid with 6% acetonitrile as mobile phase A and acetonitrile with 0.1% formic acid as mobile phase B on an Agilent 1200 HPLC system (Wilmington, DE, USA) while holding the column compartment at 60°C. The solvent method was isocratic with 98% mobile phase A and 2% mobile phase B with the flow rate set to 450 μL/min. Detection was accomplished using an AB Sciex 3200 tandem mass spectrometer (Foster city, Phenomenex Inc, Torrance, CA, USA) in the negative electrospray ionization mode (ion spray voltage: −3500 V, declustering potential: −35 V, collision energy (CE): −26 V, and collision cell exit potential (CXP): −26 V) monitoring the mass transitions m/z 221.1 → 75.1 and m/z 221.1 → 85.1 for EtG and m/z 226.1 → 75.0 for EtG-d5. EtS was monitored using the m/z 125.0 → 97.0 and m/z 125.0 → 80.0 mass transitions, whereas EtS-d5 was monitored using m/z 130.0 → 80.0 mass transition. The limits of detection (LOD) for EtG and EtS were 50 and 12.5 ng/mL, respectively; the limits of quantitation (LOQ) were 100 ng/mL (CV = 0.9%) and 25 ng/mL (CV = 3.2%), respectively; the upper limits of linearity were 10 000 ng/mL for both EtG and EtS; cutoff scores of 100 and 25 ng/mL, respectively, were applied to determine positivity.

PEth specimens were analyzed using a previously published method.15 DBS, rather than venous blood, was collected and analyzed because of its stability at room temperature and its resistance to post-collection synthesis of PEth if exposed to alcohol.1517 Three (3) standard blood spot punches (3.1 mm) were prepared for each dried human blood spot specimen, calibrator, and control. Each specimen was fortified with the addition of the isotopically labeled internal standard, PEth-d31. The punches were extracted with methanol (1 mL) and evaporated under a stream of nitrogen, and the residues were reconstituted in 1.0 mL of mobile phase A (50% 2 mM ammonium acetate: 25% acetonitrile: 25% isopropanol). Mobile phase B was 60:40 acetonitrile/2-propanol. Separation was achieved by injecting 2 μL of the extract on an Eksigent HALO C-8 column (0.5 × 50 mm, 2.7 μm particle size; AB Sciex) held at 30°C using an Eksigent Ekspert MicroLC 200 system (AB Sciex) using a solvent program starting at 30% mobile phase B, which was increased to 98% at 1.5 min, held at 98% until 3.0 min, and decreased to 30% at 3.1 min. The detector used was a Sciex 5500 tandem mass spectrometer (LC–MS/MS) in negative electrospray ionization mode (ion spray voltage: −4300 V and declustering potential: −135 V,). The method monitored a single isoform of PEth (palmitoyl/oleoyl), which is the most prevalent PEth species monitoring the m/z 701.5 → 281.3 (CE: −42 and CXP: −21) and m/z 701.5 → 255.3 (CE: −48 and CXP: −7) mass transitions for PEth and m/z 731.7 → 281.3 (CE: −46 and CXP: −23) and m/z 731.7 → 285.4 (CE: −50 and CXP: −19) mass transitions for PEth-d31. The LOD was 2 ng/mL, the LOQ was 3.2 ng/mL (CV = 18.7%), and the assay was linear up to 200 ng/mL. A cutoff of 20 ng/mL (CV = 4.3%) was applied to determine positivity.

3 |. RESULTS

On review of 1000 consecutive forensic reports, we found that 52 individuals (32 women) produced a positive test result for one or more analytes. EtG and EtS concentrations were normalized to a creatinine concentration of 100 mg/dL. Thirty-four participants carried AUD diagnoses; 28 participants were referred for an IME based on alcohol-related indications. Data are summarized for the full sample, as well as subgroups derived by AUD/referral status, in Table 1.

TABLE 1

Description and summary of results

AUD positiveAUD positiveAUD negativeAUD negative
Total (n = 52) % (n) /M (SD)EtOH+ referral (n = 21) % (n) /M (SD)EtOH− referral (n = 13) % (n) /M (SD)EtOH+ referral (n = 7) % (n) /M (SD)EtOH− referral (n = 11) % (n) /M (SD)
Sex (% women)61.5 (32)66.7(14)46.1 (6)57.1 (4)72.7 (8)
PEth20 (% detected)76.9 (40)100 (21)76.9 (10)71.4 (5)36.4 (4)
EtG100 (% detected)11.5 (6)4.8 (1)15.4 (2)0.0 (0)27.3 (3)
EtS25 (% detected)40.4 (21)9.5 (2)46.1 (6)57.1 (4)81.8 (9)
PEth (ng/mL)103.3 (96.1)105.4 (114.9)91.1 (65.1)109.0 (84.0)115.7 (95.0)
EtS (ng/mL)275.7 (477.4)301.5 (227.0)623.3 (808.4)49.8 (22.8)138.6 (131.7)
PEth—any role (%)63.5 (33)76.2 (16)77.0 (10)42.3 (3)36.4 (4)
 Essential (%)52.0 (27)71.4 (15)53.8 (7)42.9 (3)18.2 (2)
 Contributory (%)11.5 (6)4.8 (1)23.1 (3)0.0 (0)18.2 (2)

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Note: EtG was not detected with sufficient frequency to facilitate mean concentration (ng/mL) estimates and was thus omitted.

Abbreviations: AUD, alcohol use disorder; EtG, ethyl glucuronide; EtS, ethyl sulfate; PEth, phosphatidylethanol; SD, standard deviation.

3.1 |. Test comparisons

As illustrated in Table 1, EtS was more likely than EtG to produce a positive result (40.4% vs. 11.5%; P = .002). All EtG-positive results were accompanied by EtS-positive results. Thus, for purposes of comparison with PEth, EtG/EtS results were combined. Critically, agreement between PEth and EtG/EtS was low, including only 9/52 cases (17.3%). PEth produced positive results more frequently than did EtG/EtS (76.9% vs. 40.4%; P < .001).

3.2 |. AUD diagnosis and alcohol-related referrals

As illustrated in Table 1, PEth was more likely than EtG/EtS to yield positive results in participants with AUD histories (91.2% vs. 23.5%; P = .009). Conversely, EtG/EtS was more likely than PEth to produce positive results in participants without AUD histories (72.2% vs. 50.0%; P = .029). Similarly, a greater frequency of PEth-positive results was observed among individuals referred for IME on the basis of alcohol-associated indications (92.9% vs. 21.4%; P = .040), whereas EtG/EtS positive results were more common among individuals whose referrals were not alcohol associated (62.5% vs. 58.3%; P = .002).

Although subgrouping by AUD and referral status yielded insufficient sample sizes for meaningful analyses, the examination of the pattern across these groups remained informative. As summarized in Table 1, PEth was detected more often than EtG/EtS (100% vs. 9.5%) in the AUD-positive group with alcohol-related referrals, whereas the converse was true for individuals with neither an AUD history nor alcohol-related referral (81.8% vs. 36.4% for EtG/EtS and PEth, respectively).

3.3 |. Gender differences

No differences in the proportions of PEth or EtG/EtS positive results were detected between men and women (X2s ≤ 1.46, Ps ≥ .228). Similarly, no gender differences in concentrations of PEth, EtG, or EtS were detected among individuals with positive results (ts ≤ .97, Ps ≥ .335).

3.4 |. Descriptive threshold analysis

As with all accredited United States laboratories that conduct PEth testing, our laboratory has adopted a threshold of 20 ng/mL for reporting positive blood PEth results for clinical and forensic purposes.18 Because suggested EtG cutoff concentrations are context-specific (see the Discussion section) we provided a descriptive analysis of detection at alternative EtG/EtS concentration cutoffs in Figure 1. Thresholds used in the current report are included to provide a visual reference, as are alternatives represented by concentration increases of 2× (EtS50, EtG200), 3× (EtS75, EtG300), and 4× (EtS100, EtG400). The differential sensitivity of EtS relative to EtG was diminished with increased thresholds, although this observation is limited by the low frequency of EtG positive results at all thresholds.

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FIGURE 1

Proportions of positive detection at alternative ethyl glucuronide/ethyl sulfate concentration thresholds

4 |. DISCUSSION

Our principal finding was that blood PEth was an indispensable complement to urinary EtG/EtS for the detection of short- to medium-term alcohol consumption in a population of professionals who were contractually obligated to refrain from drinking. Overall, PEth20 was the biomarker that yielded the greatest number of positive results. It was far more likely to yield positive results than EtG100/EtS25 (70.2% vs. 45.6%) and was nearly twice as likely to be the only positive biomarker (54.4% vs. 29.8%). These findings were not unexpected; PEth’s half-life of several days is one to two orders of magnitude greater than those of EtG and EtS.1921 Notably, however, the advantage of PEth over EtG/EtS was found only in participants with AUD histories (whether the IME was alcohol-related). For participants without such histories, EtG/EtS was the more prevalent biomarker. We hypothesize that participants with AUDs—and who relapsed—drank more heavily than their non-AUD counterparts in the weeks before the IME but, anticipating alcohol testing, were more fastidious about abstaining for the few days before the IME. Participants without AUDs sometimes explained that they drank socially, notwithstanding their injunction to abstain, because it was their belief that they did not have a problem with alcohol.

Finally—and unexpectedly—we found that EtS was more prevalent than EtG in this population. Recently, some have argued that EtS provides little added value to EtG testing.22,23 Each of the positive EtG results was accompanied by a positive EtS result. The converse, however, was not true; of the 21 positive EtS results, only 6 (28.6%) were accompanied by positive EtG results. Moreover, EtS was more likely than EtG to be positive at every alternative cutoff concentration, with greater differences at low and very low urinary EtS concentrations. In 6/11 cases (54.5%) in which EtS was positive, but below 100 ng/mL, the participant report revealed some past-several-day alcohol consumption. Cases in which EtS was positive in the absence of detectable EtG have been reported previously.24,25 Wurst et al found that, using the same cutoffs, EtS was recovered in the urine longer after alcohol intake than EtG.24 In our study, the lower EtS cutoff contributed to the discordance.

EtG and EtS, minor metabolites of alcohol, are established direct biomarkers of acute and subacute alcohol consumption. They have limitations, however. EtG can be synthesized in urine containing E. coli and in which alcohol is present or produced in vitro (by, for example, C. albicans and glucose).26 Conversely, EtG can be degraded by β-glucuronidase-containing bacteria, including some E. coli and C. sordellii strains.26,27 Their half-lives of 2–6 h translate to relatively narrow windows of detection—up to 5 days after very heavy drinking, using very low (100 ng/mL) EtG cutoff concentrations.28 Low analyte concentrations diminish specificity, however, posing potential diagnostic dilemmas in distinguishing drinking from incidental alcohol exposures.29,30 Conversely, high cutoff concentrations diminish sensitivity, narrowing windows of detection to 1–3 days.28

Regarding EtS, there is little evidence to support specific cutoff concentrations for identifying alcohol consumption.31 The meaning of low EtS-only concentrations is uncertain. Based on limited available evidence,24,25 our contract laboratory selected an EtS cutoff concentration of 0.25 times the corresponding EtG cutoff value.

Regarding EtG, there is no general agreement on a cutoff concentration that constitutes proof of alcohol consumption. For example, Anton22 suggested EtG cutoff concentrations of 100 and 500 ng/mL for clinical (“less conservative”) and forensic (“more conservative”) purposes, respectively. Jatlow23 recommended EtG cutoff concentrations of 100 or 200 ng/mL for clinical trials. Lowe32 endorsed a 200 ng/mL cutoff for both clinical and research purposes. McDonell28 suggested a cutoff of 100 ng/mL for clinical and research purposes, and cutoffs of ≥200 ng/mL for settings in which minimizing false positive results is essential. The Substance Abuse and Mental Health Services Administration (SAMHSA) has proposed that EtG cutoff concentrations of <100 ng/mL indicate total abstinence, 100–1000 ng/mL indicate alcohol consumption or unintentional alcohol exposure, and > 1000 ng/mL confirm alcohol consumption.33

These disparate recommendations reflect the tension in balancing sensitivity and specificity concerns. Thus, cutoff concentration decision points should be context specific. Our study participants were contractually obligated to abstain from alcohol consumption and counseled to avoid sources of incidental alcohol exposure. Thus, for the purposes of this study, we chose our laboratory’s administrative cutoff concentrations of 100 and 25 ng/mL for EtG and EtS, respectively. Our evaluators, however, are mindful of the ubiquity of incidental alcohol exposures (eg, cosmetics, disinfectants, foods, and medications) and the potential consequences of false imputations of drinking (eg, being refrained from work and mandated to undergo further assessment or treatment). Consequently, absent other indicators of alcohol consumption, they are often hesitant to impute very low or low EtG (eg, <200–400 ng/mL) or EtS (eg, <50–100 ng/mL) concentrations to intentional alcohol consumption. Thus, for informational purposes, we present our data in terms of both our laboratory’s administrative cutoff concentrations and other potentially useful cutoff concentrations.

PEth is an abnormal phospholipid, synthesized from phosphatidylcholine in erythrocyte cell membranes, solely in the presence of ethyl alcohol. PEth should also be expected to provide unique information; its relatively long elimination half-life of 2.4–13.6 days34 extends the distal window of alcohol detection from the 1–5 days provided by EtG/EtS27 to 60 days or longer after chronic, heavy consumption.34

The introduction of mass spectrometric–based methods in recent years has provided vastly improved sensitivity,35 which has extended the window of PEth detection and allowed detection of lower levels of alcohol consumption. Defining an appropriate abstinence cutoff awaits further research. Pertinent to this discussion is the work of Kechagias and colleagues,36 which prospectively evaluated the ability of PEth to distinguish abstinence from moderate alcohol consumption. Forty-four subjects, all of whom self-identified as social drinkers, were randomized to abstention or moderate consumption for 3 months. PEth 16:0/18:1 was measured by LC–MSMS; the LOQ was 3.5 ng/mL. At the end of the study period, 16 of 23 subjects in the abstention group produced PEth concentrations <3.5 ng/mL, 22 of 23 produced PEth concentrations <20 ng/mL, and one produced a PEth concentration of 25 ng/mL. An important limitation was the inability to exclude surreptitious alcohol consumption.

The four accredited United States laboratories that perform PEth testing have adopted, by consensus, a common cutoff concentration of 20 ng/mL for clinical and forensic testing to distinguish beverage alcohol consumption from abstinence or incidental exposures.37 At least one of these laboratories offers a cutoff of 8 ng/mL for research testing.38,39 Recent Swiss8 and Australian40 investigators have adopted 20 and 15 ng/mL, respectively, as abstinence thresholds. Swedish laboratories use a cutoff of 35 ng/mL.37 None of these cutoffs are supported by a strong evidence base; rather they represent differing sensitivity and specificity considerations. The lower cutoffs, in particular, may lack specificity for beverage alcohol consumption. For example, it is unknown whether incidental alcohol exposures can produce suprathreshold PEth concentrations, given interindividual differences in PEth precursor homologues, phospholipase D concentrations or activities, and elimination rates.40 Also unexplored is its adequacy for monitoring alcohol consumption for individuals with liver disease. It is unknown, for example, whether endogenous alcohol and impaired first pass metabolism can result in quantifiable PEth concentrations.41

The existing literature on direct alcohol biomarker testing in the population of monitored professionals is limited to a single study. Skipper and colleagues4 performed a study of 252 participants in Alabama’s PHP. During an 8-month period in 2010–2011, 18 participants produced EtG250/EtS50-positive results on random urine drug tests. During review of the results with the participants, four affirmed that they had recently consumed alcohol. Following a discussion of a PEth “confirmatory” test that could be ordered, three additional participants admitted to recent alcohol consumption. One participant admitted to drinking after receiving a positive PEth result. The authors concluded that PEth, when used sequentially with urinary EtG/EtS, is potentially useful in discerning the meaning of “low positive” results for the urinary biomarkers. Our results confirm the conclusions of Skipper and extend their findings to demonstrate that PEth is capable of adjudicating very low EtG/EtS results. Moreover, our findings demonstrate the critical diagnostic value of PEth in participants with negative EtG/EtS results—a group that Skipper did not study because PEth testing was contingent upon positive EtG/EtS results.

Our study has notable strengths. First, our center performs a large number of IMEs, which provided a database of more than 1000 evaluations over a recent 3-year period, allowing us to recruit more than 50 participants. Second, our testing was performed by a single laboratory, which used the same analytical methods and cutoff concentrations throughout the study period.

Our study has several limitations. First, in the absence of a reliable reference standard for recent alcohol consumption in a population in which there are powerful incentives to be untruthful about alcohol use, and absent an evidence-based consensus on abstinence cutoffs for PEth and EtS, we were unable to assess the sensitivities and specificities of the biomarkers. Notwithstanding this limitation, this is the first study that examines the relative prevalence of these biomarkers in clinical-forensic contexts in which the quantity, pattern, and recency of alcohol consumption cannot be reliably ascertained and control over certain variables—chiefly the duration of time between the last drink and the collection of biological specimens—is not possible. Second, our study focused on the use of blood PEth and urinary EtG/EtS in monitoring programs for healthcare professionals. Thus, the current findings may be less generalizable to other populations. However, Florida’s monitoring programs serve more than 30 groups of licensed or certified healthcare professionals, suggesting strong generalizability to other professional monitoring populations. Moreover, recent research by Luginbuhl and colleagues on nonprofessionals being monitored during alcohol use disorder treatment has confirmed the valuable complementary functions of these biomarkers.34 Third, specimens were collected from participants who had 1–4 weeks advance notice of testing; thus cessation of drinking in anticipation of testing may have disadvantaged urinary EtG/EtS compared with random collections. Although often unavoidable in the context of IMEs in PHPs, this does constitute a limitation regarding generalizability to random drug testing contexts.

5 |. CONCLUSIONS

Blood PEth is an indispensable biomarker for identifying short- to medium-term alcohol consumption. In a population of PHP participants who were contractually obligated to abstain from drinking and who underwent recovery status IMEs, overall, PEth proved to be the most prevalent biomarker of alcohol consumption. PEth was the most prevalent biomarker in participants with AUD. Conversely, EtG/EtS was the most prevalent biomarker in participants without AUD. Our data indicate that urinary EtG/EtS and blood PEth serve complementary functions. The combination of the relatively slowly eliminated PEth and the relatively rapidly eliminated EtG and EtS improves the ability to detect past-60-day-plus alcohol consumption and may suggest possible chronologies of recent drinking.

Footnotes

CONFLICT OF INTEREST STATEMENT

Joseph Jones is an employee of United States Drug Testing Laboratories, Inc., a commercial reference laboratory that is in the business of performing the tests discussed in this article.

REFERENCES

1. Barrio P, Teixidor L, Rico N, et al. Urine ethyl glucuronide unraveling the reality of abstinence monitoring in a routine outpatient setting: a cross-sectional comparison with ethanol, self-report and clinical judgment. Eur Addict Res. 2016;22:243–248. [PubMed] [Google Scholar]

2. Staufer K, Andresen H, Vettorazzi E, Tobias N, Nashan B, Sterneck M. Urinary ethyl glucuronide as a novel screening tool in patients pre- and post-liver transplantation improves detection of alcohol consumption. Hepatology. 2011;54(5):1640–1649. [PubMed] [Google Scholar]

3. Nguyen VL, Haber PS, Seth D. Applications and challenges for the use of phosphatidylethanol testing in liver disease patients. Alcohol Clin Exp Res. 2018;42:238–242. [PubMed] [Google Scholar]

4. Bracero LA, Maxwell S, Nyanin A, Seybold DJ, White A, Broce M. Improving screening for alcohol consumption during pregnancy with phosphatidylethanol. Reprod Toxicol. 2017;74:104–107. [PubMed] [Google Scholar]

5. Afshar M, Burnham EL, Joyce C, et al. Cut-point levels of phosphatidylethanol to identify alcohol misuse in a mixed cohort including critically ill patients. Alcohol Clin Exp Res. 2017;41:1745–1753. [PMC free article] [PubMed] [Google Scholar]

6. Ulwelling W, Smith K. The PEth blood test in the security environment: what is it; why it is important; and interpretative guidelines. J Forensic Sci. 2018;63:1634–1640. [PubMed] [Google Scholar]

7. Schrock A, Hernandez Redondo A, Martin Fabritius M, et al. Phosphatidylethanol (PEth) in blood samples from ‘driving under the influence’ cases as indicator for prolonged excessive alcohol consumption. Int J Leg Med. 2016;130(2):393–400. [PubMed] [Google Scholar]

8. Schrock A, Pfaffli M, Konig S, et al. Application of phosphatidylethanol (PEth) in whole blood in comparison to ethyl glucuronide in hair (hEtG) in driving aptitude assessment (DAA). Int J Leg Med. 2016;130(6):1527–1533. [PubMed] [Google Scholar]

9. Angres DH, John A, Bettinardi-Angres K, Agarwal G. The forensic evaluation and rehabilitation of the impaired physician. Psychiatric Annals. 2019;49:487–491. [Google Scholar]

10. DuPont RL, McLellan AT, Carr G, et al. How are addicted physicians treated? A national survey of physician health programs. J Subst Abuse Treat. 2009;37:1–7. [PubMed] [Google Scholar]

11. Jarvis M, Williams S, Hurford M, et al. Appropriate use of drug testing in clinical addiction medicine. J Addict Med. 2017;11(3):163–173. [PubMed] [Google Scholar]

12. Skipper GE, Thon N, DuPont RL, et al. Phosphatidylethanol: the potential role in further evaluating low positive urinary ethyl glucuronide and ethyl sulfate results. Alcohol Clin Exp Res. 2013;37:582–1586. [PubMed] [Google Scholar]

13. Stephenson N, Dahl H, Helander A, et al. Direct quantification of ethyl glucuronide in clinical urine samples by liquid chromatography–mass spectrometry. Ther Drug Monit. 2002;24:645–651. [PubMed] [Google Scholar]

14. Dresen S, Weinmann W, Wurst FM. Forensic confirmatory analysis of ethyl sulfate—a new marker for alcohol consumption—byliquid-chromatography/electrospray ionization/tandem mass spectrometry. J am Soc Mass Spectrom. 2004;15:1644–1648. [PubMed] [Google Scholar]

15. Jones J, Jones M, Plate C, et al. The detection of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanol in human dried blood spots. Anal Methods. 2011;3:1101–1106. [Google Scholar]

16. Kummer N, Ingels AS, Wille SM, et al. Quantification of phosphatidylethanol 16:0/18:1, 18:1/18:1, and 16:0/16:0 in venous blood and venous and capillary dried blood spots from patients in alcohol withdrawal and control volunteers. Anal Bioanal Chem. 2016;408(3):825–838. [PubMed] [Google Scholar]

17. Faller A, Richter B, Kluge M, Koenig P, Seitz HK, Skopp G. Stability of phosphatidylethanol species in spiked and authentic whole blood and matching dried blood spots. Int J Leg Med. 2013;127(3):603–610. [PubMed] [Google Scholar]

18. Bakhireva N, Savich D, Raisch DW, et al. The feasibility and cost of neonatal screening for prenatal alcohol exposure by measuring phosphatidylethanol in dried blood spots. Alcohol Clin Exp Res. 2013;37:1008–1015. [PMC free article] [PubMed] [Google Scholar]

19. Dahl H, Stephanson N, Beck O, et al. Comparison of urinary excretion characteristics of ethanol and ethyl glucuronide. J Anal Toxicol. 2002;26:201–204. [PubMed] [Google Scholar]

20. Schmitt G, Droenner P, Skopp G, et al. Ethyl glucuronide in serum of human volunteers, teetotalers, and suspected drinking drivers. J Forensic Sci. 1997;42:1099–1102. [PubMed] [Google Scholar]

21. Hoiseth G, Morini L, Polettini A, et al. Blood kinetics of ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification. Forensic Sci Int. 2009;188(1–3):52–56. [PubMed] [Google Scholar]

22. Anton RF. Commentary on: ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and two clinical trials. Alcohol Clin Exp Res. 2014;38:1826–1828. [PMC free article] [PubMed] [Google Scholar]

23. Jatlow PI, Agro A, Wu R, et al. Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials. Alcohol Clin Exp Res. 2014;38:2056–2065. [PMC free article] [PubMed] [Google Scholar]

24. Wurst FM, Dresen S, Allen JP, et al. Ethyl sulphate: a direct ethanol metabolite reflecting recent alcohol consumption. Addiction. 2006;101:204–211. [PubMed] [Google Scholar]

25. Helander A, Beck O. Mass spectrometric identification of ethyl sulfate as an ethanol metabolite in humans. Clin Chem. 2004;50:936–937. [PubMed] [Google Scholar]

26. Helander A, Olsson I, Dahl H. Postcollection synthesis of ethyl glucuronide by bacteria in urine may cause false positive identification of alcohol consumption. Clin Chem. 2007;53(10):1855–1857. [PubMed] [Google Scholar]

27. Baranowski S, Serr A, Thierauf A, et al. In vitro study of bacterial degradation of ethyl glucuronide and ethyl sulfate. Int J Leg Med. 2008;122:389–393. [PubMed] [Google Scholar]

28. McDonell MG, Skalisky J, Leickly E, et al. Using ethyl glucuronide in urine to detect light and heavy drinking in alcohol dependent outpatients. Drug Alcohol Depend. 2015;157:184–187. [PMC free article] [PubMed] [Google Scholar]

29. Reisfield GM, Goldberger BA, Pesce AJ, et al. Ethyl glucuronide, ethyl sulfate, and ethanol in urine after intensive exposure to high ethanol-containing mouthwash. J Anal Toxicol. 2011a;35(5):264–268. [PubMed] [Google Scholar]

30. Reisfield GM, Goldberger BA, Pesce AJ, et al. Ethyl glucuronide, ethyl sulfate, and ethanol in urine after sustained exposure to ethanol-based hand sanitizer. J Anal Toxicol. 2011b;35(2):85–91. [PubMed] [Google Scholar]

31. Albermann ME, Musshoff F, Doberentz E, Heese P, Banger M, Madea B. Preliminary investigations on ethyl glucuronide and ethyl sulfate cutoffs for detecting alcohol consumption on the basis of an ingestion experiment and on data from withdrawal treatment. Int J Leg Med. 2012;126(5):757–764. [PubMed] [Google Scholar]

32. Lowe JM, McDonell MG, Leickly E, et al. Determining ethyl glucuronide cutoffs when detecting self-reported alcohol use in addiction treatment patients. Alcohol Clin Exp Res. 2015;39:905–910. [PMC free article] [PubMed] [Google Scholar]

33. Substance Abuse and Mental Health Services Administration (SAMHSA). The Role of Biomarkers in the Treatment of Alcohol Use Disorders, Revision; Advisory 201211:1–8. [Google Scholar]

34. Luginbuhl M, Weinmann W, Butzke I, et al. Monitoring of direct alcohol markers in alcohol use disorder patients during withdrawal treatment and successive rehabilitation. Drug Test Anal. 2019;11:859–869. [PubMed] [Google Scholar]

35. Isaksson A, Walther L, Hansson T, Andersson A, Alling C. Phosphatidylethanol in blood (B-PEth): a marker for alcohol use and abuse. Drug Test Anal. 2011;3(4):195–200. [PubMed] [Google Scholar]

36. Kechagias S, Dernroth DN, Blomgren A, et al. Phosphatidylethanol compared with other blood tests as a biomarker of moderate alcohol consumption in healthy volunteers: a prospective randomized study. Alcohol Alcohol. 2015;50:399–406. [PubMed] [Google Scholar]

37. Ulwelling W, Smith K. The PEth blood test in the security environment: what it is; why it is important; and interpretive guidelines. J Forensic Sci. 2018;63(6):1634–1640. [PubMed] [Google Scholar]

38. Fleming MF, Smith MJ, Oslakovic E, et al. Phosphatidylethanol detects moderate-to-heavy alcohol use in liver transplant recipients. Alcohol Clin Exp Res. 2017;41:857–862. [PMC free article] [PubMed] [Google Scholar]

39. Stewart SH, Koch DG, Willner IR, et al. A validation of blood phosphatidylethanol as an alcohol consumption biomarker in patients with chronic liver disease. Alcohol Clin Exp Res. 2014;38:1706–1711. [PMC free article] [PubMed] [Google Scholar]

40. Hill-Kapturczak N, Dougherty DM, Roache JD, et al. Differences in the synthesis and elimination of phosphatidylethanol 16:0/18:1 and 16:0/18:2 after acute doses of alcohol. Alcohol Clin Exp Res. 2018;42:851–860. [PMC free article] [PubMed] [Google Scholar]

41. Nguyen VL, Paull P, Haber PS, Chitty K, Seth D. Evaluation of a novel method for the analysis of alcohol biomarkers: ethyl glucuronide, ethyl sulfate and phosphatidylethanol. Alcohol. 2018;67:7–13. [PubMed] [Google Scholar]

The roles of phosphatidylethanol, ethyl glucuronide, and ethyl sulfate in identifying alcohol consumption among participants in professionals health programs (2024)
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