Phosphatidylethanol (PEth) in whole blood and carbohydrate-deficient transferrin (CDT) in serum are routinely used alcohol biomarkers of repeated high intake and harmful drinking over the preceding weeks to month. The study compared 27,293 paired measurements of PEth (PEth 16:0/18:1) and CDT (%disialotransferrin) from occupational health care testing in Sweden. PEth concentrations ranged <0.01-9.0 µmol/L (mean 0.09, median 0.36), and CDT values ranged <0.5-19.1% (mean 1.78, median 1.40). The values were significantly correlated (R = 0.64, p < 0.0001) but with substantial individual variability. Clinical classification was concordant in most cases, 66% being negative for both and 16% being positive for both at routine cutoffs (PEth >0.30 µmol/L; CDT ≥2.0%). However, PEth alone was positive in 15% and CDT alone in ∼3%. PEth identified 90% of all positive cases (i.e. by PEth and/or CDT) compared with 57% for CDT, while 47% were positive for both. Increasing the PEth cutoff to >0.50 µmol/L reduced positivity to 66%, whereas lowering the CDT cutoff to ≥1.7% increased positivity to 90%. The prevalence of positive test results increased with age. For CDT, men showed higher positivity across all age groups, while PEth scored higher for men only in those aged <30 years. In routine hospital testing (>64,000 test per biomarker), the monthly average and proportion of positive PEth values correlated with population-level alcohol consumption showing peaks during summer holidays and after Christmas-New Year, whereas no correlation was observed for CDT. In conclusion, differences between PEth and CDT are largely driven by cutoff-dependent classification rather than discordant biomarker behavior.

Suspicion of proactive drug-facilitated sexual assault (DFSA) where the perpetrator covertly administers psychoactive drugs to the victim has been reported in considerable proportions from sexual assault centers and forensic units all over the world. Substances implicated in DFSA are often referred to as 'date-rape drugs'. This study investigated toxicological findings in cases of suspected proactive DFSA presenting to the Emergency Clinic for Rape Victims in Stockholm, Sweden within 48 h of the assault. Urine samples for toxicological analysis were collected on the first visit to the clinic. During follow-up 10-14 days later, participants provided a control urine sample and reported voluntary intake of alcohol, recreational and prescription drugs in connection with the assault according to a standardized protocol. Urine samples were subjected to extensive toxicological LC-MS/MS analysis that covered common recreational drugs and >100 DFSA-associated substances. 31 out of the 55 women who presented to the clinic after a suspected proactive DFSA during the study period returned for follow-up and completed the study. Almost all women (97%) reported voluntary alcohol intake in connection with the assault, which exceeded 70 g ethanol in half of the cases. Unexpected toxicological findings were made only in five cases (16%), with the most common substance being cocaine. No typical date-rape drug was identified in cases where involuntary intake was considered likely. In conclusion, the greatest risk factor exploited by perpetrators of DFSA appears to be voluntary alcohol intoxication, while toxicological evidence of illicit drugging is rare.

BACKGROUND & AIMS:Phosphatidylethanol (PEth) is an ethanol metabolite used as a specific biomarker for recent alcohol consumption. We aimed to determine the proportion of patients with or at risk for metabolic dysfunction-associated steatotic liver disease (MASLD) who had PEth levels indicative of harmful alcohol consumption, and to assess associations between PEth levels and the risk of major adverse liver outcomes (MALOs). METHODS:We conducted a cohort study involving persons tested for PEth in Stockholm, Sweden between 2012 and 2020 (N = 46,406), including patients with various steatotic liver disease (SLD) subtypes and individuals without SLD. Cumulative incidences of MALOs were calculated for the different groups while accounting for competing risk. Cox regression was used to evaluate the association between baseline PEth levels and the incidence of MALOs. RESULTS:Among 6,377 patients with presumed MASLD, 1,294 (20%) had baseline PEth levels between 0.05 and 0.30 μmol/L (35-210 ng/ml), indicating excessive alcohol intake (MetALD), while 854 patients (13%) had values >0.30 μmol/L, indicating alcohol-related liver disease (ALD). Patients with MASLD and PEth levels between 0.05-0.30 μmol/L had similar median FIB-4 and cirrhosis prevalence as those with MASLD and PEth levels <0.05 μmol/L. However, patients with PEth levels between 0.05-0.30 μmol/L had higher cumulative incidences of MALOs compared to those with PEth levels <0.05 μmol/L. Elevated PEth levels were linked to significantly higher rates of MALOs in patients without cirrhosis, even after adjustments for age, sex, SLD subtype, and FIB-4. Patients with ALD had the highest PEth levels and worst prognosis. CONCLUSIONS:PEth is a valuable alcohol biomarker for distinguishing between SLD subtypes, especially ALD, and predicts adverse outcomes in people with and without SLD. IMPACT AND IMPLICATIONS:There is controversy regarding the various proposed steatotic liver disease (SLD) subtypes, with the most recent definition suggesting that patients with elevated alcohol consumption and MASLD should be classified as having MetALD. Here, we address this challenge by classifying patients with SLD using phosphatidylethanol (PEth), a direct and reliable biomarker for recent alcohol consumption. Our analysis of 46,406 patients revealed that PEth may be a valuable tool for distinguishing between MASLD and MetALD, and that PEth is strongly associated with the risk of liver outcomes in individuals with and without known SLD. Integrating PEth testing into routine diagnostic evaluations could enhance knowledge on the underlying pathophysiology in SLD, reduce the potential for misclassification, and ultimately improve patient outcomes by enabling clinicians to offer appropriate therapies. Further research is needed to validate these findings in other populations and to explore the potential integration of PEth into broader clinical guidelines for managing SLD.

Methamphetamine is relatively uncommon on the European drug market, but Swedish drug test laboratories repeatedly detect low methamphetamine concentrations in urine samples containing high amphetamine levels, warranting clinical evaluation for suspected polydrug use. Of 12,062 routine samples screened positive for amphetamines, 86% were confirmed positive (≥ 200 μg/L) for amphetamine, 2.1% for methamphetamine, and 4.0% for 3,4-methylenedioxymethamphetamine (ecstasy) by liquid chromatography-tandem mass spectrometry. Of the 259 methamphetamine-positive samples, 98% contained amphetamine concentrations above the reporting limit, consistent with the metabolic conversion of methamphetamine to amphetamine in the body. However, in most (69%) of these samples, the methamphetamine concentration was only < 2% of the amphetamine level, suggesting methamphetamine was not the primary drug taken. Chiral analysis of selected samples showed that after use of illicit street amphetamine with a racemic content of the l- and d-enantiomers, a similar l/d proportion was observed for methamphetamine. Similarly, in samples from patients receiving d-amphetamine-based ADHD medication, low d-methamphetamine levels were detected, even though the pharmaceutical products contained no methamphetamine. This observation, together with the parallel l/d-enantiomer distributions, supports amphetamine N-methylation as a trace, albeit quantitatively insignificant, metabolic pathway in humans. From both a clinical and forensic perspective, a low urinary methamphetamine concentration of less than a few percent of the amphetamine level therefore does not warrant further clinical evaluation for suspected polydrug use. The present findings further demonstrate that chiral analysis of both amphetamine and methamphetamine is an effective approach for distinguishing between illicit and therapeutic sources in positive screening drug tests for the amphetamines.

Recent data indicate that the use of controlled substances is increasing in working life, which can negatively affect work environment, performance, and safety. Many employers have an alcohol and drug policy that describes routines for preventive measures and early detection of illicit drug use. This often includes drug tests that provide objective information about recent use, and can be done routinely, randomly, and on suspicion. For some substances, however, a positive drug test may also result from prescription as medicine. Controlled substances that are abused and prescribed include amphetamines (ADHD medication), benzodiazepines and opiates. In a 2023 study of 23,900 urine and oral fluid drug test results from Swedish workplaces, 4.6% tested positive for one or more controlled substances. Most samples were collected in connection with random testing (40%) and new employment (36%), whereas the highest proportions of drug-positive samples were observed in cases related to accidents or incidents, or on suspicion of drug use. The highest percentage of positive random drug tests was recorded in the construction sector. The most common substances were cannabis (> 40% of cases), amphetamine (> 20%), and cocaine and benzodiazepines (> 10% each). However, many samples containing opiates (71% of cases), amphetamine (63%) and benzodiazepines (44%) were verified by a specialist trained Medical Review Officer (MRO) to be due to medical prescription, while those containing cannabis or cocaine were almost entirely due to illicit drug use. Considering the potentially negative consequences of a positive drug test in working life, an MRO should verify the results before they become final.

This study evaluated an alternative routine for reporting urinary chiral amphetamine results in assessment of attention-deficit/hyperactivity disorder (ADHD) treatment with amphetamine medications and for detecting side-use of illicit racemic amphetamine. Currently in Sweden, only enantiopure d-amphetamine-based ADHD medications (lisdexamphetamine dimesylate and dexamphetamine sulfate) are approved. It is therefore unsuitable to express the chiral result as the l/d-ratio, as before, because l-amphetamine should not be present provided treatment compliance. A new routine for LC-MS/MS chiral amphetamine testing was therefore introduced in 2020, whereby the relative proportion (%) of l-amphetamine and the total amphetamine and creatinine concentrations are reported. Evaluation of the new routine on 24,354 results from 2013 to 2023 revealed that it was useful to distinguish ADHD medication adherence from illicit drug use as the source for a positive test. The l-amphetamine proportion also reflected the enantiomeric content of the medications used. Overall, most results confirmed adherence to ADHD medication, as the l-amphetamine percentage was <1% in 76% of samples (2023) which is the recommended cutoff with enantiopure d-amphetamine medications. However, in all years, illicit drug use was indicated (>40% l-amphetamine) in 8.3%-14.5% of cases. In conclusion, this study demonstrated the clinical value and utility of a new routine for reporting urinary chiral amphetamine results to differentiate adherence to ADHD medication from illicit drug use. Unlike the l/d-amphetamine ratio, it considers differences in total amphetamine concentration and urine dilution, factors that can affect the interpretation.

This study investigated the effects of hexahydrocannabinol (HHC) and other unclassified cannabinoids, which were recently introduced to the recreational drug market, on cannabis drug testing in urine and oral fluid samples. After the appearance of HHC in Sweden in 2022, the number of posts about HHC on an online drug discussion forum increased significantly in the spring of 2023, indicating increased interest and use. In parallel, the frequency of false positive screening tests for tetrahydrocannabinol (THC) in oral fluid, and for its carboxy metabolite (THC-COOH) in urine, rose from <2% to >10%. This suggested that HHC cross-reacted with the antibodies in the immunoassay screening, which was confirmed in spiking experiments with HHC, HHC-COOH, HHC acetate (HHC-O), hexahydrocannabihexol (HHC-H), hexahydrocannabiphorol (HHC-P), and THC-P. When HHC and HHC-P were classified as narcotics in Sweden on 11 July 2023, they disappeared from the online and street shops market and were replaced by other unregulated variants (e.g. HHC-O and THC-P). In urine samples submitted for routine cannabis drug testing, HHC-COOH concentrations up to 205 (mean 60, median 27) µg/L were observed. To conclude, cannabis drug testing cannot rely on results from immunoassay screening, as it cannot distinguish between different tetra- and hexahydrocannabinols, some being classified but others unregulated. The current trend for increased use of unregulated cannabinols will likely increase the proportion of positive cannabis screening results that need to be confirmed with mass spectrometric methods. However, the observed cross-reactivity also means a way to pick up use of new cannabinoids that otherwise risk going undetected.

Aim: This retrospective study examined the prevalence of combined ethanol and cocaine use, which produces an enhanced psychoactive effect through formation of the active metabolite cocaethylene, compared to combined use of ethanol and two other common recreational drugs, cannabis and amphetamine, based on urine drug test results. Methods: The study was based on >30,000 consecutive samples from routine urine drug testing in 2020, and 2627 samples from acute poisonings in the STRIDA project (2010-2016), in Sweden. Drug testing for ethanol (i.e. ethyl glucuronide and ethyl sulfate), cocaine (benzoylecgonine), cannabis (Delta 9-THC-COOH) and amphetamine was done by routine immunoassay screening and LC-MS/MS confirmatory methods. Seven samples testing positive for cocaine and ethyl glucuronide were also analyzed for cocaethylene by LC-HRMS/MS. Results: Among routine samples for which testing of ethanol and cocaine had been requested, 43% tested positive for both substances, compared with 24% for ethanol and cannabis and 19% for ethanol and amphetamine (P < 0.0001). Among the drug-related intoxications, 60% of cocaine-positive samples were also positive for ethanol, compared to 40% for cannabis and ethanol and 37% for amphetamine and ethanol. Cocaethylene was detected (range 1.3-150 mu g/L) in all randomly selected samples testing positive for ethanol and cocaine use. Conclusions: These results, which were based on objective laboratory measures, indicated that combined ethanol and cocaine exposure was more prevalent than expected from drug use statistics. This may relate both to the common use of these substances in party and nightlife settings, and the amplified and prolonged pharmacological effect by the active metabolite cocaethylene.

Phosphatidylethanol (PEth) is a group of phospholipids that are formed in blood from the corresponding phosphatidylcholines in the presence of ethanol by action of phospholipase D. Since PEth formation requires ethanol, it is used as a specific alcohol biomarker. Use of PEth measurement in whole blood as an alcohol biomarker has risen sharply in recent years, increasing the demand for knowledge about how it should be utilized and test results evaluated. In Sweden, the use since 2013 of harmonized LC-MS analytical methods targeting the main form PEth 16:0/18:1, and confirmation of comparable test results between laboratories in the Equalis (Uppsala, Sweden) external quality control program (CV <15%), has enabled use of common decision limits. A measurable PEth result confirms ethanol exposure, but due to interindividual variations in test response to a given dose and elimination half-life during abstinence, it is not possible to indicate the exact amount or time of alcohol intake. However, a PEth level above 0.30 µmol/L (~210 µg/L) is a strong indicator of harmful drinking, while a test result below 0.05 µmol/L (~35 µg/L) excludes harmful drinking but does not confirm complete abstinence. According to current test statistics from two Swedish hospital laboratories, each performing > 60 000 routine PEth measurements annually, ~45-50% of the values were < 0.05 µmol/L, ~23-24% between 0.05-0.30 µmol/L, ~16-19% between 0.30-1.0 µmol/L, and ~10-12% > 1.0 µmol/L. Some PEth results even exceeded 10 µmol/L.

Phosphatidylethanol (PEth) are membrane molecules formed from phosphatidylcholine and ethanol through transphosphatidylation catalyzed by phospholipase D. Measurement of the main PEth form 16:0/18:1 is used as a specific and sensitive alcohol biomarker, since its formation requires ethanol, it accumulates in the blood upon repeated ethanol exposure, and it is only slowly eliminated during abstinence. PEth formation correlates with alcohol intake at the population level, albeit with considerable inter-individual variation as for the half-life during withdrawal. Over the past decade, the use of PEth has increased significantly and the applications have broadened. In Sweden, routine decision limits and the interpretation of test results for PEth were harmonized in 2013, using < 0.05 µmol/L (∼35 µg/L) as the recommended lower reporting limit and values > 0.30 µmol/L (∼210 µg/L) to indicate regular high alcohol intake. Routine test results show a large variation with about half being < 0.05 µmol/L and some even exceeding 10 µmol/L. In 2013, an external quality assessment (EQA) scheme for PEth 16:0/18:1 measurement in whole blood was also started (Equalis, Uppsala, Sweden), presently involving 56 laboratories from 13 countries. The agreement of PEth results between the laboratories has gradually improved to a CV < 15%. The current clinical and scientific information suggests that PEth values below the lower reporting limit (typically ∼0.03-0.05 µmol/L, or ∼20-35 µg/L) indicates sobriety or only low or occasional alcohol consumption, while regular high alcohol intake at levels corresponding to harmful drinking is required in most cases to reach PEth values > 0.30 µmol/L.

Drug Testing and AnalysisVolume 15, Issue 7 p. 791-792 LETTER TO THE EDITOR Comment on the upper cutoff level for the alcohol biomarker phosphatidylethanol (PEth) for the assessment of alcohol consumption in forensic practice Frank Musshoff, Corresponding Author Frank Musshoff [email protected] orcid.org/0000-0002-9613-0525 Forensisch Toxikologisches Centrum GmbH, Munich, Germany Correspondence Frank Musshoff, Forensisch Toxikologisches Centrum GmbH, Dessauerstr. 13-15, 80992 Munich, Germany. Email: [email protected]Search for more papers by this authorMichael Böttcher, Michael Böttcher MVZ Labor Dessau GmbH, Dessau-Roßlau, GermanySearch for more papers by this authorMatthias Graw, Matthias Graw Institute of Legal Medicine, Ludwig-Maximilians-University of Munich, Munich, GermanySearch for more papers by this authorGisela Skopp, Gisela Skopp Forensisch Toxikologisches Centrum GmbH, Munich, GermanySearch for more papers by this authorJasna Neumann, Jasna Neumann MVZ Labor Dessau GmbH, Dessau-Roßlau, GermanySearch for more papers by this authorGudrun Høiseth, Gudrun Høiseth Department of Forensic Sciences, Oslo University Hospital, Oslo, NorwaySearch for more papers by this authorAnders Helander, Anders Helander orcid.org/0000-0001-7480-8078 Department of Laboratory Medicine, C1:74, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author Frank Musshoff, Corresponding Author Frank Musshoff [email protected] orcid.org/0000-0002-9613-0525 Forensisch Toxikologisches Centrum GmbH, Munich, Germany Correspondence Frank Musshoff, Forensisch Toxikologisches Centrum GmbH, Dessauerstr. 13-15, 80992 Munich, Germany. Email: [email protected]Search for more papers by this authorMichael Böttcher, Michael Böttcher MVZ Labor Dessau GmbH, Dessau-Roßlau, GermanySearch for more papers by this authorMatthias Graw, Matthias Graw Institute of Legal Medicine, Ludwig-Maximilians-University of Munich, Munich, GermanySearch for more papers by this authorGisela Skopp, Gisela Skopp Forensisch Toxikologisches Centrum GmbH, Munich, GermanySearch for more papers by this authorJasna Neumann, Jasna Neumann MVZ Labor Dessau GmbH, Dessau-Roßlau, GermanySearch for more papers by this authorGudrun Høiseth, Gudrun Høiseth Department of Forensic Sciences, Oslo University Hospital, Oslo, NorwaySearch for more papers by this authorAnders Helander, Anders Helander orcid.org/0000-0001-7480-8078 Department of Laboratory Medicine, C1:74, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenSearch for more papers by this author First published: 30 December 2022 https://doi.org/10.1002/dta.3432Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1Luginbühl M, Wurst FM, Stöth F, Weinmann W, Stove CP, van Uytfanghe K. Consensus for the use of the alcohol biomarker phosphatidylethanol (PEth) for the assessment of abstinence and alcohol consumption in clinical and forensic practice (2022 Consensus Basel). Drug Testing Anal. 2022; 14(10): 1800-1802. doi:10.1002/dta.3340 2Ulwelling W, Smith K. The PEth blood test in the security environment: what it is; why it is important; and interpretative guidelines. J Forensic Sci. 2018; 63(6): 1634-1640. doi:10.1111/1556-4029.13874 3Helander A, Hansson T. Nationell harmonisering av alkoholmarkören PEth [National harmonization of the alcohol biomarker PEth]. Lakartidningen. 2013; 110(39–40): 1747-1748. PMID: 24245431. 4 Deutsche Gesellschaft für Verkehrspsychologie (DGVP) und Deutsche Gesellschaft für Verkehrsmedizin (DGVM). Urteilsbildung in der Fahreignungsbegutachtung - Beurteilungskriterien, 4. Bonn, Germany: Auflage, Kirschbaum Verlag; 2022. 5Schröck A, Pfäffli M, König S, Weinmann W. 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. doi:10.1007/s00414-016-1394-4 6Weinmann W, Schröck A, Wurst FM. Commentary on the paper of Walther L. et al.: phosphatidylethanol is superior to CDT and GGT as an alcohol marker and is a reliable estimate of alcohol consumption level. Alcohol Clin Exp Res. 2016; 40(2): 260-262. doi:10.1111/acer.12946 7Helander A, Hermansson U, Beck O. Dose–response characteristics of the alcohol biomarker phosphatidylethanol (PEth)—a study of outpatients in treatment for reduced drinking. Alcohol Alcohol. 2019; 54(6): 567-573. doi:10.1093/alcalc/agz064 8Isaksson A, Walther L, Hansson T, Andersson A, Stenton J, Blomgren A. High-throughput LC-MS/MS method for determination of the alcohol use biomarker phosphatidylethanol in clinical samples by use of a simple automated extraction procedure-preanalytical and analytical conditions. J Appl Lab Med. 2018; 2(6): 880-892. doi:10.1373/jalm.2017.024828 9Årving A, Høiseth G, Hilberg T, et al. Comparison of the diagnostic value of phosphatidylethanol and carbohydrate-deficient transferrin as biomarkers of alcohol consumption. Alcohol Clin Exp Res. 2021; 45(1): 153-162. doi:10.1111/acer.14503 10Neumann J, Beck O, Böttcher M. Phosphatidylethanol, ethyl glucuronide and ethanol in blood as complementary biomarkers for alcohol consumption. J Mass Spectrom Adv Clin Lab. 2021; 22: 3-7. doi:10.1016/j.jmsacl.2021.09.005 11Høiseth G, Hilberg T, Trydal T, Husa A, Vindenes V, Bogstrand ST. The alcohol marker phosphatidylethanol is closely related to AST, GGT, ferritin and HDL-C. Basic Clin Pharmacol Toxicol. 2022; 130(1): 182-190. doi:10.1111/bcpt 12Helander A, Böttcher M, Dahmen N, Beck O. Elimination characteristics of the alcohol biomarker phosphatidylethanol (PEth) in blood during alcohol detoxification. Alcohol Alcohol. 2019; 54(3): 251-257. doi:10.1093/alcalc/agz027 13Gnann H, Weinmann W, Thierauf A. Formation of phosphatidylethanol and its subsequent elimination during an extensive drinking experiment over 5 days. Alcohol Clin Exp Res. 2012; 36(9): 1507-1511. doi:10.1111/j.1530-0277.2012.01768.x Citing Literature Volume15, Issue7July 2023Pages 791-792 ReferencesRelatedInformation

Mitragyna speciosa, known as kratom, is a tropical tree native to Southeast Asia that has long been used to increase energy and in traditional medicine. Kratom leaves contain several indole alkaloids including mitragynine, mitraciliatine, speciogynine, and speciociliatine, which have the same molecular formula and connectivity, but different spatial arrangements (i.e., diastereomers). A routine liquid-chromatographic-high-resolution mass-spectrometric (LC-HRMS) multi-analyte method for addictive and herbal drugs in urine did not separate mitragynine from speciogynine and speciociliatine. Separation and individual measurement of the four diastereomers was possible with an improved LC method. All diastereomers were detected in 29 patient urine samples who tested positive for mitragynine with the routine method, albeit at variable absolute amounts and relative proportions. The presence of all diastereomers rather than individual substances indicated that they originated from the intake of kratom (i.e., plant material). Speciociliatine dominated in most samples (66%), whereas mitragynine and mitraciliatine were the highest in 17% each. A kratom product (powdered plant material) marketed in Sweden contained all diastereomers with mitragynine showing the highest level. In Sweden, there are signs of an increasing use of kratom in society, based on the results from drug testing, the number of poisons center consultations on intoxications, and customs seizure statistics. Because there may be health risks associated with kratom use, including dependence, serious adverse reactions, and death, analytical methods should be able to identify and quantify all diastereomers. In Sweden, this is important from a legal perspective, as only mitragynine is classified, whereas the other three diastereomers, and kratom (plant material), are not.

Acute poisoning involving toxic alcohols other than ethanol is not uncommon. Poisonings from drinking isopropanol are rarely life threatening, whereas methanol and ethylene glycol without prompt treatment cause severe metabolic acidosis, organ damage, and death, mainly due to toxic metabolites. Rapid identification of the type of alcohol responsible for the poisoning requires access to 24/7 toxicological service. The analysis of alcohols is usually done with gas chromatographic (GC) methods, which are not always available at smaller or medium-sized hospitals. As a complement to GC methods, reliable enzymatic oxidation procedures are now available for the analysis of ethanol, methanol, and ethylene glycol. The present study showed good agreement (r2 = 0.996) between the results of methanol analysis with a new enzymatic method (Catachem Inc.) and with GC over the clinically relevant concentration range (1-50 mmol/l). Moreover, high concentrations of ethanol (up to 80 mmol/l), ethylene glycol (to 40 mmol/l), isopropanol (to 100 mmol/l) or acetone (to 20 mmol/l) did not interfere with the analytical results for methanol. Toxicological analysis of the two most dangerous alcohols (methanol and ethylene glycol) can now be done with rapid and specific enzymatic methods, which makes it possible to diagnose and treat poisoned patients at smaller regional hospitals.

Background and purpose High alcohol intake is associated with increased risk of postoperative complications. Alcohol cessation intervention is recommended prior to elective surgery. We investigated short- and long-term effects of perioperative intensive alcohol intervention in relation to acute ankle fracture surgery. Patients and methods 70 patients requiring ankle fracture surgery and consuming ≥ 21 drinks weekly (1 drink = 12 g ethanol) were randomized to a manual-based 6-week intensive standardized alcohol cessation program, the Gold Standard Program (GSP-A), or treatment as usual (TAU), on the day of operation. GSP-A included 5 personal meetings, patient education, and motivational and pharmacological support (alcohol withdrawal prophylaxis, B vitamins, and low-dose disulfiram). Complications requiring treatment were measured after 6 weeks and 1 year. Alcohol intake was validated by biomarkers. Quality of life (QoL) was measured by the SF-36. Hospital costs were obtained from the National Hospital Costs Register. Results Postoperatively, complete alcohol cessation was higher in the GSP-A than in the TAU group (18/35 vs. 5/35, number needed to treat = 3, p ≤ 0.001), but not lowrisk consumption in the long term (10/35 vs. 7/33, p = 0.5). Number of complications in the short and long term (12/35 vs. 14/33, 16/35 vs. 18/33), the SF-36 score, or hospital costs in the short and long term (€6,294 vs. €8,024, €10,662 vs. €12,198), were similar between the groups. Interpretation Despite an effect on alcohol cessation and a positive tendency as regards the other outcomes, the postoperative complications, QoL, and costs were similar. Better perioperative strategies for acute surgical patients with high alcohol intake therefore need to be developed.

Workplace alcohol and drug testing is increasingly used at employment, for regular checks, and in case of accident, incident, or suspicion of drug exposure. The test results provide valuable objective information about drug use in the society. At the Karolinska University Laboratory (Stockholm, Sweden), the number of samples from drug testing in the workplace has quadrupled in the last decade. Almost all urine samples are tested for amphetamines (amphetamine, methamphetamine and MDMA), benzodiazepines (prescribed substances), cannabis, cocaine and opiates, and some also for alcohol (i.e. the metabolites ethyl glucuronide and ethyl sulfate) and drugs such as tramadol and oxycodone. The proportion of samples that test positive for one or more drugs has increased steadily in recent years to over 5%. Substances commonly detected are, in order of appearance, cannabis, amphetamines (amphetamine and MDMA), benzodiazepines, opiates (mainly codeine and only few due to heroin use), and cocaine. Other common substances are alcohol, tramadol, and oxycodone, but these are only tested for in a limited, and possibly selected, proportion of samples. After an MRO has reviewed the positive laboratory results, about 30% of cases are excluded mainly due to legal prescription as medicine. In 2020, the proportion of positive test results decreased, possibly due to reduced access to illicit drugs during the corona pandemic. In summary, results from drug testing in the workplace indicate that illicit use of drugs shows an increasing trend in Sweden.

During routine urine drug testing for cannabis use targeting delta-9-tetrahydrocannabinol carboxylic acid (delta-9-THC-COOH) at the Karolinska University Laboratory in Sweden, an unknown interfering peak was observed in the liquid-chromatographic-tandem mass-spectrometric (LC-MS/MS) confirmative analysis. The peak showed the same exact mass and most abundant fragments as delta-9-THC-COOH but a slightly shorter retention time, thereby not fulfilling all requirements for a positive identification. The analytical results suggested that it was a similar compound, and with access to reference material, it could be identified as the double bond isomer delta-8-THC-COOH. Delta-8-THC has recently become popular as a recreational drug, although its legality varies and is sometimes unclear. In Sweden, all THC isomers are classified substances. The slight difference in retention times was sufficient to distinguish the THC-COOH isomers in the routine LC-MS/MS method, but another LC method allowed better peak separation and individual quantification. At the Karolinska University Laboratory, delta-8-THC-COOH was first observed in April 2020, and the highest incidence was noted in June 2020 when it was present in 5.3% of all THC-COOH-positive samples. The incidence later decreased to today only occasional findings. Large differences in the relative presence of the isomers in the urine samples indicated different origin, for example, synthetically produced pure delta-8-THC, or mixtures of both THC isomers formed during combustion of cannabidiol (CBD). In conclusion, the appearance of delta-8-THC and other isomers on the recreational drug market risks causing analytical and medico-legal problems, due to confusion with delta-9-THC.