Ethyl Glucuronide Research Articles

Rapid and Effective Determination of Ethyl Glucuronide in Hair by Micro Extraction by Packed Sorbent (MEPS) and LC-MS/MS.

Ethyl glucuronide (EtG) in hair is a reliable biomarker of alcohol consumption habits. Due to its small concentration incorporated into hair, analytical methods sensitive enough to reliably quantify EtG in this matrix are required. Sample preparation is critical in hair analysis, especially for EtG, for which extraction efficiency and matrix effect can strongly influence the results; furthermore, miniaturized methods are sought, to reduce solvent use and times of sample preparation. A micro extraction by packed sorbent (MEPS) procedure coupled to a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for quantitation of EtG in human hair samples. Fifty milligrams of hair samples were cut into snippets and extracted in water. The cleanup of the extract was carried out by using a MEPS syringe packed with anion exchange sorbent (SAX); all parameters for conditioning, washing, loading and eluting steps were optimized and the eluted aqueous volume was directly injected in the LC-MS/MS system operating in the negative ionization mode. The method was fully validated assessing LOD, LOQ, calibration curve, repeatability, accuracy, matrix effect and carryover. The method was subsequently applied to QCs and authentic hair samples. The developed MEPS method is quick and effective, with low solvent purchase and discard costs, allowing the differentiation between social drinkers and chronic excessive alcohol consumers, according to the cut-offs established by the Society of Hair Testing (SoHT).

B-161 Liquid chromatography/mass spectrometry analysis of ethyl glucuronide and ethyl sulfate using a perfluorophenyl stationary phase

Abstract Background Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are minor metabolites of ethanol that are excreted in urine. These two metabolites are often tested for to determine if an individual has recently consumed alcohol. EtG and EtS are very polar analytes, which make them difficult to chromatograph using reversed-phase chromatography. These analytes often elute early, which can lead to irreproducible results. When EtG and EtS are analyzed by LC/MS with a mobile phase that contains formic acid, the signal of these two analytes can be suppressed. This leads to increased LOQ and cutoffs. We examined the perfluorophenyl (PFP) stationary phase for its utility in analyzing EtG and EtS. This stationary phase has been shown to have greater retention of polar compounds than C18 reversed-phase columns. In addition, we compared the effect of formic acid to acetic acid on the separation. Methods Urine samples containing EtG and EtS were diluted 10:1, using 50mM acetic acid or 0.1% formic acid, into a 96-well microtiter filter plate containing a 0.2micron filter. Internal standards were added to the microtiter plate containing the urine samples. The samples were filtered through the filter plate and analyzed by LC/MS using the PFP column (50 x 2.7micron) with a 50mM acetic acid or 0.1% formic acid/acetonitrile mobile phase. The analytes were detected using negative mode ionization. The total analysis time was 4.5minutes. Results EtG and EtS showed improved retention using the PFP column. Retention times for EtG and EtS were 0.75 and 1.20 minutes respectively using the PFP column, compared to 0.4 and 0.3 minutes using the C18 column. The greater retention time improved the LOQ for both analytes.The LOQ for EtS and EtG were determined to be 125 and 250 ng/mL, respectively. Greater retention of EtG was observed by switching the modifier from formic acid to acetic acid. The retention time increased from 0.45 to 0.75 minutes. There was less signal suppression using acetic acid in place of formic acid. Improvement in peak shape was observed when the injection volume was reduced to 5microliters. The method was validated over a range of 250 to 10000 ng/mL for EtG and 125 to 5000 ng/mL for EtS. Acceptable linearity was obtained for both analytes. Accuracy was performed at three concentration levels. All three levels demonstrated acceptable accuracy with the difference between the measured and expected concentration being with in 20% of each other. Conclusions The PFP stationary can be used to test EtG and EtS. This stationary phase gave greater retention of EtS and EtG. The use of acetic acid improved the limit of detection by decreasing the ion suppression, which decreased the limit of detection. The assay was accurate and precise for both analytes, demonstrated in the validation.

B-260 Prevalence and Relative Distributions of Major Phosphatidylethanol (PEth) Homologs in a Large-Scale Clinical Study

Abstract Background Ethanol abuse remains a significant public health challenge in the United States. Detection of ethanol exposure is crucial for preventive, diagnostic, and therapeutic endeavors. Phosphatidylethanol (PEth) is a specific and direct ethanol biomarker. Compared to other metabolites, such as ethyl glucuronide and ethyl sulfate in urine (average 2-3 days), PEth in blood has a longer window of detection (average 1-2 weeks). Among the known 48 PEth homologs, PEth 16:0/18:1 (POPEth) and PEth 16:0/18:2 (PLPEth) are the most abundant species accounting for 37% to 46% and 26% to 28%, respectively. PLPEth is synthesized at a greater rate than POPEth, but POPEth has a longer half-life than PLPEth. The purpose of this study was to understand the prevalence and levels of POPEth and PLPEth in a large number of clinical specimens. Methods Briefly, lavender-top whole blood specimens were diluted with isotopically labeled internal standard (IS) in an organic buffer to precipitate proteins on an automated Hamilton platform. The mixture was centrifuged, and a supernatant portion isolated for injection onto a Sciex QTRAP 5500 liquid chromatography tandem mass spectrometry (LC-MS/MS) system using electrospray ionization (ESI) in negative mode. The assay was fully validated under CLIA regulations for lab developed tests: the analytical measurement range (AMR) was 10-400 ng/mL; the administrative reporting threshold for PEth positivity was 20 ng/mL based on clinical literature and a consensus among other United States laboratory methods. Results Precision of 4 QC levels was evaluated with between-run CV% (n=25) ranging from 1.6-6.3%, and accuracy across the AMR was achieved with 87-110%. No significant matrix effects were observed; variation in different whole blood specimens was corrected with IS normalization. No significant interferences were observed from 137 commonly seen prescription and nonprescription drugs and 6 other PEth homologs. Of the clinical specimens, most (20,833, 71.3%) were negative (<20 ng/mL) for both analytes. Meanwhile, 8,222 specimens (28.3%) were positive with either POPEth, or PLPEth or both ≥ 20ng/mL. There were 150 specimens excluded from the statistics due to interference challenges. Interestingly, 757 specimens (2.6%) were PLPEth negative and POPEth positive (mean value 40.1 ng/mL). Conversely, 62 specimens (0.2%) were POPEth negative and PLPEth positive (mean value 24.6 ng/mL). Among the specimens with both POPEth and PLPEth levels within the AMR, the average POPEth/PLPEth ratio was 1.4 supporting the overall prevalence of higher POPEth concentrations than PLPEth. However, the POPEth/PLPEth ratio varied widely, from 0.3 to 8.8, reflecting patient differences in PEth metabolism patterns. Conclusions To help verify probable ethanol abstinence, we have developed, validated, and deployed a high-throughput clinical assay for the major PEth homologs, POPEth and PLPEth. In a retrospective analysis of 29,205 clinical specimens: 71.3% of results were consistent with abstinence; 28.3% of the results were positive suggesting moderate alcohol consumption within the last 1-2 weeks. With POPEth most prevalent, yet variation observed, there were 62 specimens with PLPEth positive and negative for POPEth. This clinical PEth study including both POPEth and PLPEth provides greater sensitivity to identify ethanol exposure than only testing a single homolog.

B-291 Validation of a Simple Qualitative Immunoassay for 21 Drugs of Abuse in Meconium on a Single Biochip Array

Abstract Background Drugs use during pregnancy is a major social and medical issue, which may lead to significant pre- and post-natal complications, such as preterm birth and newborn mortality. Exposed newborns may have long-term behavioral, cognitive, and developmental problems. Accurate detection of in utero drug exposure is crucial for timely medical intervention for the newborn and the mother. Meconium is the ‘gold standard' matrix for detection of drugs in newborn which reflects drug exposure during pregnancy. This study aims to develop and optimize a clinical assay for simultaneous screening of 21 drugs in meconium using a custom biochip array. Methods Custom biochip array (Randox Laboratories Ltd.) included 21 discrete test regions (DTRs) for amphetamine, methamphetamine, opioids/opiates (targeting morphine, oxymorphone, oxycodone, hydrocodone, 6-monoacetyl morphine, tramadol, buprenorphine, fentanyl, and methadone), phencyclidine (PCP), cocaine (targeting benzoylecgonine), benzodiazepines (targeting oxazepam, lorazepam, and clonazepam), zolpidem, barbiturates (targeting phenobarbital), ethyl glucuronide, methylphenidate, and marijuana metabolite (targeting Delta-9-Carboxy-Tetrahydrocannabinol [THC-COOH]). Patient samples were obtained from the residual meconium samples that had been previously used for other tests. Blank meconium samples were spiked at in-house cutoff, negative and positive assay control levels. All samples were extracted in specimen diluent using Biotage® Lysera and centrifuged. The supernatant was analyzed on a fully automated Randox Evidence+® Analyzer. A robotic arm pipetted 60 µL sample on to a biochip and then the analyzer performed a competitive chemiluminescent immunoassay. The results were generated as relative light units (RLUs). Results The sample results were determined to be “positive” or “negative” based on average RLU of cutoff controls for each analyte on an assay. The intra-assay (CV ≤ 15%) and inter-assay (CV ≤ 18%) precision was 100% agreement for positive and negative controls and there was no observed carryover for any of the analytes. The sample recovery was excellent with minimal to no matrix suppression for all analytes. Accuracy was performed by comparing spiked analyte results from Randox Evidence+® Analyzer with the expected results and all the spiked samples matched (positive or negative). When authentic patient or spiked results were compared with external laboratory test results, some discordant results were obtained. However, the discrepancies could be explained based on the different cutoffs (e.g., the Randox assay had lower cutoffs) or the known assay cross reactivities within the analytes of same class. These deviations did not affect clinical utility of the assay. Conclusions We validated a novel and simple qualitative chemiluminescent immunoassay in meconium using a custom biochip array. Unlike other routine screening/ELISA methods, which require separate assays for detection of similar drug targets, the custom biochip array offers a convenient, rapid and efficient method that utilizes only a single sample preparation for the screening of all 21 drug targets. Therefore, this technology has potential to be utilized as high-throughput screening assay. Like all qualitative assays, the limitation of this test is that all positive results will need to be assessed quantitatively for a definitive interpretation.

Simultaneous determination of four ethanol biomarkers in blood: avalidated method for use in forensic toxicology in 257 postmortem samples

Purpose: Ethyl alcohol is the most widely and legally available intoxicating substance. However, excessive consumption is associated with numerous negative social consequences, including the potential for significant health risks. Rapid and simple diagnosis of alcohol use is necessary to initiate appropriate and effective treatment and is critical in forensic toxicological analysis. Ethanol biomarkers have clinical utility in the detection, diagnosis, and treatment of alcohol use disorders. Materials and Methods: An analytical method for the simultaneous determination of four different alcohol biomarkers ethyl glucuronide (EtG), ethyl sulphate (EtS), N-acetyltaurine (NAcT), and 16:0/18:1-phosphatidyl ethanol (PEth) in blood samples from forensic cases was developed, validated and verified for the accurate monitoring of alcohol abuse and dependence. Analyses were performed using a liquid chromatography-mass spectrometry system. Results: 257 blood and vitreous samples were collected from 255 male and 2 female subjects aged 16-80 years (average 44±14.82) from the Forensic Medicine Council of Turkey and analyzed for ethanol biomarkers and calculated ethanol concentrations. A total of 257 blood samples were found to contain ethanol, with concentrations ranging from 12.0 to 444.0 mg/dL. Vitreous concentrations ranged from 23 mg/dL to 597 mg/dL. The limit of detection (LOD) for EtG, EtS, NAcT, and PEth were 3.1, 3.9, 7.3, and 5.7 ng/mL respectively in blood samples. The limit of quantification (LOQ) for EtG, EtS, NAcT, and PEth were 7.8, 8.4, 18.3, and 13.1 ng/mL, respectively in blood samples. Conclusion: The method has potential in forensic toxicology as an invaluable tool for the accurate and simultaneous identification of biomarkers of alcohol use and dependence in different biological samples.

Alcohol Use among Young Women in Kampala City: Comparing Self-Reported Survey Data with Presence of Urinary Ethyl Glucuronide Metabolite.

This study sought to determine the level of concordance between self-reported alcohol use and the presence of its urinary ethyl glucuronide (EtG) metabolite in women living in urban Kampala. In 2023, we recruited 300 young women, ages 18 to 24 years, to participate in a prospective cohort study across three sites in urban Kampala (i.e., Banda, Bwaise, and Makindye) to examine the mechanistic pathways of mental illness. As part of the baseline assessment, participants were asked to complete a research assistant-administered survey and to provide a urine sample to screen for 16 different substances and/or their metabolites, including EtG. Overall, 58% (n = 174) reported to have ever consumed alcohol and 23% (n = 68) to have used it in the past month. Among the 300 women, 10% (n = 30) had EtG levels in their urine sample and of these, 40% (n = 12) reported to have never consumed alcohol, using a self-reported survey (p = 0.035). Recent alcohol use was relatively low among the women in this study. However, the discordance between self-reported alcohol use and the presence of EtG presents concerns about the accuracy of self-reported alcohol use. Additional research is needed to contextualize self-reported alcohol use, social desirability, and the implications for alcohol prevention and intervention strategies for young women in urban Kampala.

Consumption of Sylimarin, Pyrroloquinoline Quinone Sodium Salt and Myricetin: Effects on Alcohol Levels and Markers of Oxidative Stress-A Pilot Study.

Alcohol abuse is one of the most common causes of mortality worldwide. This study aimed to investigate the efficacy of a treatment in reducing circulating ethanol and oxidative stress biomarkers. Twenty wine-drinking subjects were investigated in a randomized controlled, single-blind trial (ClinicalTrials.gov. Identifier: NCT06548503; Ethical Committee of the University of Padova (HEC-DSB/12-2023) to evaluate the effect of the intake of a product containing silymarin, pyrroloquinoline quinone sodium salt, and myricetin (referred to as Si.Pi.Mi. for this project) on blood alcohol, ethyl glucuronide (EtG: marker for alcohol consumption) and markers of oxidative stress levels (Reactive Oxygen Species-ROS, Total Antioxidant Capacity-TAC, CoQ10, thiols redox status, 8-isoprostane, NO metabolites, neopterin, and uric acid). The effects of the treatment versus placebo were evaluated acutely and after 1 week of supplementation in blood and/or saliva and urine samples. Si.Pi.Mi intake reduced circulating ethanol after 120 min (-33%). Changes in oxidative stress biomarkers, particularly a TAC (range +9-12%) increase and an 8-isoprostane (marker of lipidic peroxidation) decrease (range -22-27%), were observed too. After the administration of Si.Pi.Mi, the data seemed to suggest a better alcohol metabolism and oxidative balance in response to wine intake. Further verification is requested.

A novel method for the simultaneous determination of drugs of abuse, ethyl glucuronide and synthetic opioids in human hair through a single digestion, purification and analysis in LC-MS/MS

Polydrug use is a serious health and social problem worldwide. Over the past several years, there has been an increasing tendency to combine narcotics, alcohol, sedatives, and/or stimulants. To the traditional drugs of abuse and alcohol, an increase of new abuse drugs such as synthetic opioids has been added. In the current study, the development and validation of an innovative and fast analytical procedure has been presented to determine drugs of abuse, ethyl glucuronide and synthetics opioids in 30 mg of human hair through a single digestion, purification and analysis in LC-MS/MS. A combine simple preparation of hair sample followed to a single chromatographic run of 10 min has been proposed. A full validation for 54 target analytes for the parameters of selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, recovery, and dilution integrity was successful completed. The method was linear in different ranges with r values of at least 0.990; the value to the validated LLOQ values were in the range 0.1–100 pg/mg. The method offered satisfactory precisions (CV<15 % and accuracy ± 20 %). In conclusion, a significant reduction in the overall times of the analytical procedure and the reduction of consumables costs make this method extremely advantageous and undoubtedly useful in routine laboratory workflow analyses and open the way to the prospect of a further implementation which also includes other classes of xenobiotics.

The international prevalence of prenatal alcohol use obtained via meconium biomarkers: A systematic literature review.

Fetal alcohol exposure is a growing public health concern. However, ascertaining its true extent remains challenging as maternal self-reports may lack validity. Increasingly, interest has turned to more objective measures of prenatal alcohol use (PAU) of which one, meconium, is recognized as a valuable tool. This review assesses both the international prevalence of PAU obtained using meconium biomarkers in general maternity populations and, when feasible, the level of agreement between meconium biomarkers and self-reported PAU. A systematic literature search for studies reporting the prevalence of PAU, as determined by meconium biomarker testing, was conducted using multiple electronic databases from 1990 to 2023. Seventeen studies were identified for inclusion and evaluated for methodological quality. Using fatty acid ethyl esters (FAEEs) meconium biomarkers, PAU prevalence varied from 2.4% to 44%. Rates based on EtG (ethyl glucuronide) analysis ranged from 0% to 16.3%, and EtS (ethyl sulfate) analysis from 7.8% to 16.7%. Studies were of moderate quality with high heterogeneity. Prevalence rates based on self-report data ranged from 0% to 46.4%. When reported, none of the reviewed studies identified agreement between meconium-based and self-report-based PAU prevalence rates. Using both self-reports to detect early pregnancy alcohol use, and meconium biomarkers to detect the occurrence of alcohol use later in pregnancy, may provide a more complete picture of PAU prevalence. Furthermore, research is warranted to develop stringent guidance on the ascertainment, storage, analysis, and reporting required in this field.

Evaluation and comparison of sensitivity of alcohol biomarkers PEth, EtG and EtPa in civil cases in England 2022–2023

This study details trends in direct alcohol biomarker concentrations from civil cases within the United Kingdom (UK). Our subject cohort in this study related to family law litigation, where an individual was subject to an alcohol monitoring order by the court. This monitoring was conducted by quantification of alcohol biomarkers Phosphatidlyethanol (PEth) in dried blood spots (DBS) and Ethyl Glucuronide (EtG) and Ethyl Palmitate (EtPa) from hair segments. In total 298 PEth cases predominantly from the South East of England during the period July 2022 to August 2023 were analysed for alcohol biomarkers in DBS and hair. Subjects alcohol intake was classified as abstinence/low alcohol consumption, moderate or excessive alcohol consumption, based on a combination of Society for Hair Testing and PEth Net guidelines. Our results indicate that 33 % of PEth concentrations were consistent with excessive alcohol use (>200 ng/mL DBS), with 36 % consistent with social or moderate alcohol use (20–200 ng/mL DBS). In relation to EtG and EtPa 23 % and 31 % of subjects were classified as excessive alcohol users respectively. This study indicates that DBS sampling of PEth is a more sensitive predictor of alcohol use, in particular, at differentiating between moderate and excessive alcohol use compared to EtG and EtPa testing in hair. The authors suggest that increased frequency in the sampling of PEth in DBS (multiple occasions per month) may provide a more accurate assessment and simplification of the interpretation criteria of alcohol patterns rather than the combined hair testing and DBS sampling that are typically requested by UK courts.

Using umbilical cord tissue to identify prenatal ethanol exposure and co-exposure to other commonly misused substances.

Substance misuse during pregnancy can result in a variety of poor pregnancy outcomes. Objective data reporting the prevalence of neonates born with ethanol metabolites (evidence of prenatal ethanol exposure) in their fluids or tissues are limited. A secondary analysis of umbilical cord tissue specimens received for routine toxicological analysis was conducted. Prevalences of ethyl glucuronide (EtG), a long-term direct ethanol biomarker, were determined using a new laboratory tool, LDTD-MSMS. Additionally, other commonly misused substances were determined using routine procedures. Of 12,995 specimens, 238 (1.8%) specimens contained EtG. Concentrations of EtG ranged from 5 ng/g to 6679 ng/g (median 47 ng/mg; IQR: 16 ng/g, 203 ng/g). Of those 238 EtG-positive specimens, nearly 58% (N = 138) contained additional substances or metabolites. Self-report of substance use during pregnancy is under-reported. We have demonstrated co-exposure of substances with ethanol is higher than previous reports.

Delirium in Neurocritical Care: Uncovering Undisclosed Psychotropic Substance and Medication Use and Stress Exposure by Hair Analysis.

In intensive care, delirium is frequent, prolongs the stay, increases health care costs, and worsens patient outcome. Several substances and medications as well as stress can impact the risk of delirium; however, assessment of previous exposure to psychotropic agents and stress by self-reports or third-party information is not always reliable. Hair analysis can be used to objectively assess medication and substance use (including chronic alcohol consumption), and allows for the determination of stress-related long-term changes in steroid hormones and endocannabinoids. Consecutive adult patients with acute brain injury admitted to the neurocritical care unit were included. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit. Liquid chromatography coupled with tandem mass spectrometry was used to investigate psychoactive substances and medications, ethyl glucuronide, steroid hormones, and endocannabinoids in hair samples. Univariable and multivariable analyses were used to reveal any associations with the occurrence of delirium. Of 50 consecutive patients, 21 (42%) were diagnosed with delirium. Detection of antipsychotics or antidepressants in hair was more frequent in patients with delirium (antidepressants: 43% vs. 14%, p = 0.040; antipsychotics: 29% vs. 0%, p = 0.021). These patients also displayed higher ethyl glucuronide levels (p = 0.049). Anandamide (AEA) concentrations were higher in patients with delirium (p = 0.005), whereas oleoylethanolamide (p = 0.045) and palmitoylethanolamide (PEA) (p = 0.017) concentrations were lower in patients with delirium. Backward stepwise logistic regression analysis revealed antidepressants and AEA/PEA to be independent relevant predictors of delirium. Hair analysis provides crucial and otherwise unattainable information regarding chronic stress and the use of psychotropic substances and medications. Undisclosed antidepressant/antipsychotic use or intense chronic alcohol consumption is susceptible to treatment (continuation of medication or provision of low-dose benzodiazepines in case of alcohol). Chronic stress can be evaluated using stress markers and endocannabinoids in hair, potentially allowing for personalized delirium risk stratification and preventive measures.

Identification of Alcohol Use Prior to Major Cancer Surgery: Timeline Follow Back Interview Compared to Four Other Markers

Background: The postoperative complication rate is 30–64% among patients undergoing muscle-invasive and recurrent high-risk non-muscle-invasive bladder cancer surgery. Preoperative risky alcohol use increases the risk. The aim was to evaluate the accuracy of markers for identifying preoperative risky alcohol. Methods: Diagnostic test sub-study of a randomized controlled trial (STOP-OP trial), based on a cohort of 94 patients scheduled for major bladder cancer surgery. Identification of risky alcohol use using Timeline Follow Back interviews (TLFB) were compared to the AUDIT–C questionnaire and three biomarkers: carbohydrate-deficient transferrin in plasma (P–CDT), phosphatidyl-ethanol in blood (B–PEth), and ethyl glucuronide in urine (U–EtG). Results: The correlation between TLFB and AUDIT–C was strong (ρ = 0.75), while it was moderate between TLFB and the biomarkers (ρ = 0.55–0.65). Overall, sensitivity ranged from 56 to 82% and specificity from 38 to 100%. B–PEth showed the lowest sensitivity at 56%, but the highest specificity of 100%. All tests had high positive predictive values (79–100%), but low negative predictive values (42–55%). Conclusions: Despite high positive predictive values, negative predictive values were weak compared to TLFB. For now, TLFB interviews seem preferable for preoperative identification of risky alcohol use.

An incentive-based text-messaging intervention to reduce maternal alcohol use during pregnancy and lactation in South Africa (MaRISA study): Findings from a single-arm pilot study.

South Africa has the highest rate of fetal alcohol spectrum disorders (FASD) globally. As with alcohol use during pregnancy, alcohol consumption while breastfeeding adversely impacts infant development. We pilot tested an incentive-based text-messaging intervention to reduce alcohol use during pregnancy and lactation in South Africa. A single-arm pilot trial was conducted over 3 months in healthcare facilities in Cape Town, South Africa. Pregnant and breastfeeding participants tested positive for recent alcohol use by urinalysis. The three-month intervention had two components, contingency management of alcohol abstinence confirmed by urinalysis twice weekly and weekly health-related text messaging from an evidence-based brief intervention. We collected twice weekly urine samples for measurement of ethyl glucuronide (EtG), an alcohol biomarker, and measures of self-reported alcohol and drug use, violence exposure, and mental health at six weeks and three months post-enrollment. Sixty participants were enrolled, of whom 31 were pregnant and 29 lactating. The number of days with four or more drinks in the past month decreased from 9 days at baseline, on average, to 1-3 days (p-value range: 0.144-0.010) at follow-up timepoints. There were statistically significant increases in the proportions of participants with alcohol-negative urine tests (p < 0.001). The percentages of participants breastfeeding while using alcohol decreased from baseline to the end of 3 months in the overall sample and among those enrolled postpartum, though these were not significant (p-value range: 0.255-0.147). Maternal depression scores also decreased among participants enrolled postpartum (p = 0.054). Emotional abuse by the main partner, but neither physical nor sexual abuse, significantly decreased at both follow-ups in the overall sample (p = 0.032) and among participants enrolled while pregnant (p = 0.015). This study is among the first to pilot test an incentive-based text-messaging intervention for maternal alcohol use and other outcomes such as depression and violence exposure. Further testing is warranted in a well-powered, randomized controlled trial.

Sensitivity, specificity, and discordance with self-report of nail sample testing for alcohol and cannabis

BackgroundNails accumulate the alcohol metabolite, ethyl glucuronide (ETG), and the cannabis metabolite, carboxy- delta-9-THC over 3–6 months. Few studies have examined nail toxicology testing’s sensitivity and specificity and the agreement between nail testing and self-reported alcohol and marijuana use. MethodsIn an ongoing clinical trial, 1101 veterans completed initial telephone questionnaires and were then asked to mail nail clippings for substance use analysis. We examined sensitivity and specificity of ETG and carboxy- delta-9-THC in nails compared to self-report of alcohol use patterns (the AUDIT-C) and substance-related harms (alcohol and THC subscales of the ASSIST). We then examined factors associated with discordance between nails and self-report. ResultsAlmost two-thirds (707/1101) of respondents mailed in nail clippings. Those with returned nails were disproportionately married, white race, older, and less depressed. At a threshold of 8pg/mg, sensitivity was only.50 to detect risky alcohol use and.49 to detect alcohol-related issues. Sensitivity for marijuana issues was only.61. Specificity was greater than.77 for all measures.Factors associated with positive nails/negative self-report (i.e. false positives) for risky alcohol use on the Audit-C included more pain and being unmarried; false positive nails for alcohol-related issues on the ASSIST were associated with being unmarried and non-Hispanic ethnicity. False positive nails for THC-related issues on the ASSIST were associated with being African American, Hispanic, and having had legal issues. ConclusionsAt standard cut-offs, nail measures had low sensitivity and higher specificity. The groups who disproportionately submit positive nails/negative self-report could have substance use patterns not adequately captured by self-report, inaccurate self-report due to social pressures, or distinct drug metabolism.

Retrospective Data Analysis Reveals Unusual Metabolism Pattern of Ethanol in Pediatrics as Compared to Adult and Geriatric Populations.

About 95% of consumed ethanol is metabolized by oxidative pathways. Less than 1% is metabolized via nonoxidative pathways: glucuronidation, sulfation, and the formation of fatty acid esters of ethanol. In neonates, the glucuronidation pathway has been reported to be underdeveloped but matures with age. This work compared the test results of patients' random urine samples submitted to our facility for ethyl glucuronide (EtG) and ethyl sulfate (EtS) measurements across pediatric and adult populations. Test results (n = 63 498) from urine samples tested for EtG and EtS by quantitative liquid chromatography-tandem mass spectrometry at our facility were utilized for this study. EtG and EtS concentrations were compared across the age partitions 0 to 17 years (pediatric), 18 to 80 years (adult), and 81 to 100 years (geriatric). Eight pediatric patients from a tertiary academic hospital contributed clinical context via abstracted clinical information. Across the individual age partitions, 60% to 65% of patients had both EtG and EtS present in urine. Approximately 5% to 10% of patients had only EtG, and 25% to 35% had neither metabolite present. The lowest percentages (<1.5%) had EtS present in the absence of EtG. Markedly, no pediatric patients had only EtS present; compared to the adult population, this was statistically significant (Fisher exact test, P = 0.025). From the data presented in this work, EtG is more prevalent relative to EtS in urine samples of patients assessed for ethanol exposure.

Prevalence of Psychoactive Substance Use During Pregnancy in Argentine Women: A Pilot Study Testing Maternal Hair.

The use of psychoactive substances (PSs) during pregnancy is a major public health concern because of their increasing prevalence worldwide. This study examined the understudied issue of gestational PS consumption in a cohort of Argentine delivering mothers. A cross-sectional pilot study involving 51 women receiving delivery care was conducted at the Santa Rosa Hospital in La Pampa, Argentina. Information on maternal sociodemographic characteristics, pregnancy history, and drug use was obtained through standardized interviews. Maternal hair samples were analyzed for alcohol, tobacco, licit, illicit, and prescription substance biomarkers using ultra-high-performance liquid chromatography high-resolution mass spectrometry and gas chromatography mass spectrometry. During pregnancy, 49.0% of participants reported alcohol consumption, 25.5% reported tobacco use, and 23.5% reported cannabis use. Hair samples from 56.9% of the women were positive for illicit PSs, with the most frequent being cocaine (41.2%) and cannabis (15.7%). Among the women, 47.1% consumed alcohol during pregnancy. Of the 24 women with hair ethyl glucuronide ≥5 pg/mg, 33.3% drank until the end of gestation and 58.3% started a social drinking habit in the second half. The analysis also detected prescription substances (anticonvulsants, antidepressants, methadone, opioids, antihistamines, antiemetics, and analgesics), caffeine (70.6%), lidocaine, and levamisole, some of which were cocaine or opioid adulterants. This is the first study to objectively assess the consumption of licit and illicit PSs during pregnancy in Argentina. In contrast to most nearby countries, cocaine was the most detected illicit PS in this cohort of Argentine delivering women. This finding highlights the importance of regular monitoring of local trends in PS use during pregnancy.

Evaluation of harmful drinking among professional drivers by direct ethanol biomarkers and its relation with psychological distress

Objective This study aimed to evaluate the alcohol consumption among professional truck and bus drivers using direct ethanol biomarkers, and to explore its relationship with anxiety, depression, and stress. Methods The assessment of potential harmful drinking was conducted through the measurement of direct biomarkers: phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulfate (EtS), using dried blood spots (DBS). Additionally, self-reported data from the Alcohol Use Disorders Identification Test (AUDIT-C) were used. Emotional states, including depression, anxiety, and stress, were evaluated using the Depression, Anxiety, and Stress Scale (DASS-21). Results A total of 97 drivers participated in the study, with the majority being male (96%) and identified as truck drivers (75.3%). Among them, 43.3% reported working more than 10 h daily. The majority of volunteers exhibited normal levels of stress (81.4%), anxiety (83%), and depression (86.6%). According to the AUDIT-C assessment, 30.9% were categorized as having a moderate risk, while 11.3% were deemed to be at high risk for harmful alcohol consumption behavior. Ethyl glucuronide (EtG) and ethyl sulfate (EtS) levels, indicating recent ethanol consumption, were detected in 14.4% of the drivers. In contrast, the long half-life metabolite PEth (16:0-18:1) was present in 88.7% of the volunteers. A moderate correlation (rs = 0.45, p < .01) was observed between PEth levels and AUDIT-C scores. The Receiver Operating Characteristic (ROC) curve, utilizing a PEth threshold of ≥ 59.0 ng ml−1, displayed 78% sensitivity and 73% specificity in effectively distinguishing high risk for alcohol intake. Notably, no significant associations were found between alcohol consumption and levels of stress, depression, and anxiety. Conclusions The study findings indicate a noteworthy proportion of drivers engaging in regular alcohol consumption alongside a demanding workload. Notably, PEth measurements highlighted an underreporting within the AUDIT-C self-reports. These results lend robust support for the utilization of biomarkers in assessing alcohol consumption patterns among drivers.

Is there a relationship between abuse of alcohol and illicit drugs seen in hair results?

Combined use of alcohol and illicit drugs is a serious health and social problem. In this study, it was examined, whether a relationship between alcohol and drug abuse can be ascertained by comparison of alcohol marker and drug concentrations in hair. In the frame of a social support system for families with parental abuse of illicit drugs, hair samples were analyzed between 2011 and 2022 for methadone, heroin (6-acetylmorphine), cocaine, amphetamine, ecstasy (MDMA), cannabinoids (THC), and the alcohol markers ethyl glucuronide (EtG) and ethyl palmitate (EtPa). For 1314 hair samples from adolescent and adult family members, the hair results show a prevalence of combined occasional or regular drug use and social or abusive alcohol use of 41%-60% except heroin (35%). The drug concentrations were statistically compared in the three categories of abstinence or moderate drinking, social drinking, and alcohol abuse. For the most frequently detected drug cocaine (n = 703), a significant increase of the concentrations with rising alcohol consumption was found. The frequent detection of cocaethylene proved the preferred simultaneous intake of both substances. For THC (n = 489), no significant difference between the alcohol consumer groups was seen. Concerning the less frequently detected methadone (n = 89), 6-acetylmorphine (n = 92), amphetamine (n = 123), and MDMA (n = 105), no clear trend between drug and alcohol marker results was determined. It is concluded that the evaluation of hair results is an appropriate way to study the extent of combined drug-alcohol consumption and complements other studies based on acquisition of consumption data by interview or questionnaire.

Sex differences and driving impairment related to psychoactive substances

Objective The first aim of the study was to identify sex differences in the use of psychoactive substances among subjects with a previous driving under the influence (DUI) episode. The secondary objective was to propose specific strategies for medico-legal improvements. Methods This was a retrospective observational study that took place between June 1, 2019, and August 31, 2023. It was conducted on DUI subjects examined for reinstatement of their driver’s license using an integrated medico-legal and toxicological approach. Ethyl glucuronide (EtG) and illicit psychoactive substances were determined from hair samples. We performed descriptive statistical analyses for the entire sample as well as separately by sex. Additionally, we conducted binary logistic regression analyses separately for males and females to identify protective/risk factors associated with previous road accidents and judgments of unfitness to drive due to excessive alcohol consumption (EtG ≥ 30 pg/mg). Results The study included 2,221 subjects, comprising 1,970 men and 251 women. Men exhibited a higher prevalence of tobacco, alcohol, and illicit psychoactive substance use. Women were more frequently co-users of alcohol and psychoactive substances and involved in road accidents at the time of DUI. Among the men, being married or having a partner was found to be a protective factor concerning past traffic accidents. For both sexes, a DUI episode with a blood alcohol concentration (BAC) exceeding 1.5 g/L or the co-ingestion of alcohol and drugs was identified as a risk factor for road accident involvement. For men, smoking more than 20 cigarettes per day and, for women, having a DUI episode with a BAC over 1.5 g/L were the main factors indicating unfitness to drive, as determined through high hair EtG levels (> 30 pg/mg). Women with a previous history of road accidents were less likely to have EtG levels of 30 pg/mg or more. Conclusions The study confirmed sex differences in subjects with a previous DUI episode. A BAC exceeding 1.5 g/L or the simultaneous use of alcohol and drugs at the time of DUI necessitate careful assessment of both men and women seeking driver’s license reinstatement. In women, a BAC exceeding 1.5 g/L is considered a risk factor for a subsequent judgment of unfitness to drive. The medico-legal assessment should also involve a thorough investigation of smoking habits in men, as these habits could be related to an increased risk of excessive alcohol consumption.