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A streamlined LC-MS/MS method utilizing protein precipitation and filtration extraction was developed to consolidate analyses for drug-facilitated crime (DFC), postmortem investigations, and driving under the influence of drugs (DUID) testing. Fifty-seven target drug and metabolite analytes eluted in under 6-minutes and compromised of GHB precursors (1), hallucinogens (3), muscle relaxants (3), anticonvulsants (7), antidepressants (20), antihistamines (5), antipsychotics (11), antihypertensives and alpha-adrenergics (3), analgesics and anesthetics (3), and miscellaneous (1) in blood (quantitatively) and urine (qualitatively). Limits of detection were set to meet the more challenging sensitivity requirements for DFC, and are therefore also suitable for postmortem investigations, and other forensic casework, including DUID. Comprehensive ASB/ANSI validation was performed, and applicability studies examined 72 proficiency test blood and urine samples, along with 9,206 unique blood and urines samples from 5,192 authentic forensic cases that resulted in 11,961 positive analytes in samples. By expanding the analytical reach across multiple drug classes through a unified approach and screening a wider number of drugs, the technique can identify substances that might have previously evaded detection, thereby enhancing laboratory efficiency by minimizing the need for multiple tests. When combined with a recently developed in-house method, this integrated testing strategy meets the testing requirements outlined in ASB/ANSI standards and recommendations for DFC, postmortem, and Tier 1 DUID analyses.

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OBJECTIVE: Driving under the influence of drugs (DUID) is a growing traffic safety problem in many countries. It is estimated that 5 to 10% of medicinal drugs may impair driving due to their side effects. Despite the high number of medicinal drugs prescribed in Iran, there is a lack of a database that could provide specialized information regarding medicinal drugs and driving. Therefore, the present study aimed to design, develop, and evaluate a database for informing the general public, drivers, and healthcare providers regarding driving-impairing medicines. METHODS: The Drugs-and-traffic-safety (DATS) database, which has been developed by Road Traffic Injury Research Center (RTIRC), was designed using Java, HTML, JavaScript and MySql database. After completing the testing process, pharmaceutical data (i.e., generic and brand names, route of administration, anatomical classification, etc.), the level of influence of medicinal drugs on driving, and driving-related recommendations based on the level of influence for consumers were entered into the database. A cross-sectional study, and a qualitative study as semi-structured interviews and expert panels were conducted in different target groups to evaluate the DATS. Finally, the evaluation results were used to improve the database. The quantitative and qualitative data were analyzed using SPSS 25.0 and MAXQDA-10, respectively. RESULTS: The DATS was the only web-based database that could be accessed online via different browsers. The database included information about 1,255 medicinal drugs, and their influence on driving was shown with four colors, i.e., green (insignificant or no effect), yellow (mild effect), orange (moderate effect), and red (severe effect). The database was designed in multiple languages, which could enable users to search for medicinal drug names in both Persian and English. Based on the quantitative results, the mean score of the DATS was 75.10 ± 16.01 (out of 100) from the public viewpoint, indicating that the users were relatively satisfied with the database. Some themes and subthemes were extracted from the qualitative section of the study which revealed the users found DATS a practical, useful, and user-friendly tool. CONCLUSION: Considering the positive feedback of users about DATS in the quantitative and qualitative evaluations, implementing DATS in Iran could provide useful advice in terms of the influence of medicinal drugs on driving to the public and traffic users. Therefore, it can raise public awareness of the risk of driving under the influence of medicinal drugs.

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Driving under the influence of alcohol and other drugs is a prominent safety concern in New Zealand and across the world. While alcohol testing is routinely performed for drivers involved in hospitalisation crashes, testing for other drugs is often not undertaken. The present study refers to 530 traffic crashes that occurred from October 2019 to January 2020 on New Zealand roads. The blood samples from 550 drivers who were injured in a crash and were admitted to a hospital (66% of all drivers involved in these crashes), previously tested for drugs and/or alcohol, were retested for a wider range of drugs. Alcohol above the applicable limit was found to be present in 38% of hospitalised drivers, while other drugs of interest were found in 47% of hospitalised drivers. Binary logistic regression was used to predict the presence of drugs of interest for a crashed driver using previous offence data. A driver having at least one prior drink and drug driving offence is 61% more likely to be positive for a drug of interest when involved in a crash. Similarly, a driver having at least one prior non-traffic drug offence is 4.7 times more likely to be positive for at least a drug of interest when involved in a crash. While the presence of a drug or drugs cannot be presumed to have played a role in the occurrence of the crash, this study has provided a unique and comprehensive picture of the presence of various drugs present in New Zealand drivers' blood. It is recommended to consider standardising drug testing on all blood specimens taken in relation to a serious injury or fatal crash. This procedure is not only of interest for information purposes but may importantly inform appropriate charging decisions.

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GHB is an endogenous short-chain organic acid presumably also widely applied as a rape and knock out drug in cases of drug-facilitated crimes or sexual assaults (DFSA). Due to the endogenous nature of GHB and its fast metabolism in vivo, the detection window of exogenous GHB is however narrow, making it challenging to prove use of GHB in DFSA cases. Alternative markers of GHB intake have recently appeared though none has hitherto been validated for forensic use. UHPLC-HRMS based screening of blood samples for drugs of abuse is routinely performed in several forensic laboratories which leaves an enormous amount of unexploited data. Recently we devised a novel metabolomics approach to use archived data from such routine screenings for elucidating both direct metabolites from exogenous compounds, but potentially also regulation of endogenous metabolism and metabolites. In this paper we used UHPLC-HRMS data acquired over a 6-year period from whole blood analysis of 51 drivers driving under the influence of GHB as well as a matched control group. The data were analyzed using a metabolomics approach applying a range of advanced analytical methods such as OPLS-DA, LASSO, random forest, and Pearson correlation to examine the data in depth and demonstrate the feasibility and potential power of the approach. This was done by initially detecting a range of potential biomarkers of GHB consumption, some that previously have been found in controlled GHB studies, as well as several new potential markers not hitherto known. Furthermore, we investigate the impact of GHB intake on human metabolism. In aggregate, we demonstrate the feasibility to extract meaningful information from archived data here exemplified using GHB cases. Hereby we hope to pave the way for more general use of the principle to elucidate human metabolites of e.g. new legal or illegal drugs as well as for applications in more global and large scale metabolomics studies in the future.

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Driving under the influence of drugs (DUID) remains a subject of concern worldwide, and its increasing trend is likely to continue. Therefore, there is a constant need for reliable on-site drug tests to identify drugged drivers during roadside patrols. Performance and reliability of four on-site drug tests were evaluated among a high number of DUID cases in Germany. Results of oral fluid (OF) (RapidSTAT® and DrugWipe® 6S) and urine (DrugScreen® 5TK and 7TR) test devices were compared with corresponding serum/plasma results obtained by confirmation analyses in consideration of recommended analytical limits for substances pertaining the annex of the German Road Traffic Code ('Straßenverkehrsgesetz', StVG) s. 24a (2). Overall, the screening devices performed well for individual drugs; however, none of the test devices assessed in this study fulfilled the ROSITA-1 criteria (sensitivity, specificity ≥ 90% and accuracy ≥ 95%) for all substances. Our data demonstrated that both urine tests showed high sensitivities for most compounds. DrugWipe® 6S (94%) and RapidSTAT® (93%) revealed high sensitivities, especially for amphetamine screening. Poor specificities (<90%) and accuracies (<95%) were observed for all tests except for low-prevalent substances (e.g., opiates). For drug testing in OF, Δ9 -tetrahydrocannabinol (THC) still seems to be a compound of concern due to poor sensitivity (RapidSTAT®, 77%; DrugWipe® 6S, 85%), although the results indicate improvements compared with previously reported data. Although the obtained data indicate reliable detection for some substances, deployment of trained police officers is inevitable to identify DUID suspects by signs of recent use and recognising impairment.

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Drug driving is a serious problem worldwide that can increase the risk of road crashes. This systematic review seeks to identify factors associated with drug driving (i.e., driving after consuming drugs other than alcohol) to highlight gaps in existing knowledge and inform the design of more effective countermeasures. A search of the literature was conducted for the period January 1, 2005 to July 31, 2021 using six different databases. The search protocol followed PRISMA guidelines and was registered in PROSPERO (#CRD42021234616). Studies that met inclusion criteria compared drug drivers with either non-drug drivers, alcohol-only drivers or drug drivers from an earlier time period, to identify factors specifically associated with drug driving, rather than common to all drivers. Two hundred and nineteen publications met the inclusion criteria and were included within the review. Based on the findings, a logic model was developed that presents the factors associated with drug driving. Various sociodemographic, psychosocial and legal factors emerged as the main factors associated with illegal drug driving. At the sociodemographic and psychological levels, drug drivers were more likely to be single, young males who often drive after using cannabis and who score high on sensation-seeking and impulsivity scales. The key social factor found to be associated with drug driving was peer acceptance/disapproval of the behaviour. At the legal level, the review suggested that the effectiveness of current enforcement approaches to drug driving vary among jurisdictions around the world due to differences in the level of perceived certainty of apprehension and the chances of punishment avoidance. Future research into the anticipated and actual rewards for drug driving is needed to inform the development of more effective countermeasures.

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Driving under the influence of alcohol and drugs (DUID) is a major field of study to improve road safety. In Switzerland, during controls whether or not they follow an accident, the police can request toxicological analysis targeted either on alcohol only (ALC cases), or on drugs and alcohol (DUID cases). To evaluate both the drugs consumption on the road and whether or not these requests are well correlated with toxicological results, we built a database recording 4003 offenders (3443 males, 550 females) over a two-year period (2018-2019) in Western Switzerland. ALC case samples were then analyzed to target other substances than ethanol. We found one or more psychoactive drugs in 89% of DUID cases and alcohol alone was found in 56% of ALC cases. In ALC cases, alcohol alone was found in 72% of non-accident cases and in 52% of accident cases. This highlights an influence of accident context, inducing a too high suspicion of alcohol after accidents, and therefore an underestimation of the prevalence of other drugs. The most frequently detected drugs in DUID cases were cannabinoids (58%), ethanol (30%), cocaine (21%), benzodiazepines (11%), amphetamines (7%), opiates (6%), and antidepressants (5%). For the ALC cases, the drugs found were ethanol (84%), cannabinoids (13%), benzodiazepines (9%), antidepressants (6%), opiates (5%), cocaine (4%), methadone (3%), and amphetamines (1%). Prescription drugs, such as benzodiazepines, were common in accidents (22%) but rare in non-accidents DUID cases (5%). Thus, these drugs highly impact driving skills while being hard to suspect. This is of first concern as prescription drugs are largely found in poly-drug consumption, especially in combination with alcohol in accident cases. This emphasizes the emerging issue of prescription drugs and should motivate a strategy of prevention focused on the noxious effect of combining alcohol and prescription drugs on driving skills.

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In forensic toxicology, amphetamine intoxications represent one of the most common case groups and present difficult questions for toxicologists. Estimating the time of consumption and the current influence of the stimulant is particularly difficult when only total amphetamine concentrations are considered. Stereoselective analysis and the consideration of metabolites can provide valuable information to facilitate interpretation. An enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection of amphetamine, norephedrine and 4-hydroxyamphetamine was developed. Validation showed satisfactory selectivity, sensitivity, linearity (0.5-250 ng/mL), precision and accuracy for all enantiomers. The method was applied to a collective of 425 forensic serum samples and 30 serum samples from psychiatric inpatients stating their last time of amphetamine consumption. Norephedrine and 4-hydroxyamphetamine were detected more frequently at higher amphetamine concentrations and at lower amphetamine (R)/(S) concentration ratios, possibly indicating recent consumption. Mean (R)/(S) ratio of amphetamine was 1.14, whereas higher ratios (mean 1.36) were found for amphetamine concentrations below 100 ng/mL. The (R)/(S) ratios of psychiatric inpatients significantly correlated with the reported time intervals to last consumption. The use of amphetamine (R)/(S) ratios and the simultaneous detection of metabolites are promising factors that can facilitate estimation of consumption time and current impairment.

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Driving under the influence of drugs (DUID) is a serious global problem and poses a public health risk. With new psychoactive substances (NPS) entering the illicit drug market several years ago, a significant number of highly potent and harmful drugs have become easily available and the use of these substances may impair a person's ability to drive a vehicle safely. Since NPS are not usually covered in routine toxicological analyses used in DUID investigations, only little is known about their prevalence. To gather more information on the prevalence of NPS in cases of impaired driving, a retrospective study was conducted to determine the prevalence of these drugs in blood samples of DUID suspects in southern Germany. A total of 837 blood samples, which were collected in the German federal states Baden-Württemberg and Bavaria in 2017 and 2018, were reanalyzed for designer stimulants and synthetic cannabinoids by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). For the analysis of synthetic cannabinoids, a more sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method was additionally used. A total of 14 cases (1.6%) tested positive for NPS. Designer stimulants were detected in two cases (0.2%) and synthetic cannabinoids were found in 12 cases (1.4%). The rather low prevalence rate of 1.6% estimated in this study suggests that driving under the influence of NPS does not play a large role in southern Germany. Nonetheless, in all cases in which the psychophysical impairment cannot be explained by routine toxicological findings, a screening for NPS should additionally be performed.

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A high-throughput UHPLC-MS/MS method for the most frequently found compounds; tetrahydrocannabinol (THC), amphetamine, methamphetamine, MDMA, clonazepam, diazepam, nordiazepam, oxazepam, alprazolam, nitrazepam, morphine, and codeine, in driving under the influence of drugs (DUID) cases in whole blood, is presented. Automated sample preparation by 96-well supported liquid extraction (SLE) plates with ethyl acetate + heptane (80 + 20, v/v) as organic solvent was carried out on a Freedom Evo 200 platform from Tecan. An aliquot of 100 µL whole blood was used. Sample preparation time for 96 samples was 1.5 h. Compounds were separated with gradient elution on a C18 column (50 × 2.1 mm, 1.7 µm) with a mobile phase consisting of 5 mM pH 10.2 ammonium formate and methanol. The run time was 4.5 min and 1 µL was injected on an Acquity UPLC I-Class system with a Xevo TQS tandem-quadrupole mass spectrometer in multiple-reaction monitoring mode (MRM) from Waters. Isotope labelled, 13C, internal standards (ISs) were used for all compounds except for alprazolam and morphine, which had deuterated analogs. Quantification was carried out with calibrators without whole blood matrix. Full validation was carried out according to international guidelines, and a new approach for evaluation of process efficiency (PE) has been presented. Linear or quadratic weighted (1/x) calibration curves were used with R2 ≥ 0.999. The method showed satisfactory deviations ±16% when compared to the existing methods, and satisfactory agreement with proficiency testing control samples (z-score -1.6 to 1.8, n = 16 samples). The precision, estimated as the relative standard deviation (RSD) of the concentration difference between results from two independent analyses of authentic whole blood samples, was ≤7.2% in antemortem and ≤9.3% in postmortem samples. Recovery was ≥85% for all the compounds, except morphine ≥62% and THC ≥ 50%. PE was satisfactory for all the compounds with low variation in IS response, RSD ≤ 16% (THC 27%) in antemortem samples and ≤34% (THC 66%) in postmortem samples. To the best of our knowledge, this is the first automated 96-well SLE UHPLC-MS/MS method developed for the simultaneous determination of these 12 compounds in whole blood covering the concentration ranges found in forensic samples. The method has been used in routine work during the last ten months, analysing about 9900 antemortem and 1000 postmortem whole blood samples, and has proven to be robust and reliable.

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BACKGROUND: The effects of drugs on driving performance should be checked with drug concentration in the brain and at the same time with the evaluation of both the behavioural and neurophysiological effects. The best accessible indicator of this information is the concentration of the drug and/or metabolites in blood and, to a certain extent, oral fluid. We sought to review international studies on correlation between blood and oral fluid drug concentrations, neurological correlates and cognitive impairment in driving under the influence of drugs. METHODS: Relevant scientific articles were identified from PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE up to April 2017. RESULTS: Up to 2010, no epidemiological studies were available on this matter and International scientists suggested that even minimal amounts of parent drugs in blood and oral fluid could affect driving impairment. More recently, epidemiological data, systematic reviews and meta-analysis on drugged drivers allowed the suggestion of impairment concentration limits for the most common illicit drugs. These values were obtained comparing driving disability induced by psychotropic drugs with that of established blood alcohol limits. Differently from ethyl alcohol where both detection methods and concentration limits have been well established even with inhomogeneity of ranges within different countries, in case of drugs of abuse no official cut-offs have yet been established, nor any standardized analytical protocols. CONCLUSION: Multiple aspects of driving performance can be differently affected by illicit drugs, and even if for few of them some dose/concentration dependent impairment has been reported, a wider knowledge on concentration/impairment relationship is still missing.

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OBJECTIVE: This study examined the time from law enforcement dispatch to the first blood draw in cases of driving under the influence (DUI) vehicular homicide and a subset of DUI vehicular assault cases in Colorado in 2012. Laboratory toxicology results were also examined to understand the implications of delays in blood draws in cases of driving while under the influence of marijuana's delta-9-tetrahydrocannabinol (THC). METHODS: Colorado court records were reviewed and information regarding charges, presence of alcohol and/or drugs, time of law enforcement contact and blood draw, crash location, and other contextual factors were identified. The distributions of first blood draw times were studied by charge and by responding law enforcement agency. Toxicology data from a different cohort of DUI traffic arrests in Colorado and Washington were examined to determine the proportion of blood tests for THC that were above specified legal limits in those states. RESULTS: The average time from law enforcement dispatch to blood draw in cases of vehicular homicide and vehicular assault was 2.32 h (SD ± 1.31 h), with a range of 0.83 to 8.0 h and a median of 2.0 h. Data from DUI traffic arrests found that between 42 and 70% of all cannabinoid-positive traffic arrests tested below 5 ng/ml THC in blood, which is the legal limit in Colorado and Washington. CONCLUSION: Given the current delays to blood testing in cases of arrests for vehicular homicide and vehicular assault in Colorado, many blood tests are unlikely to confirm that drivers who are impaired from smoking marijuana have THC levels above established legal limits.

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OBJECTIVE: UR-144 [(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)-methanone] is a synthetic cannabinoid, which has been detected in many "legal highs" seized from the global drug market since the beginning of 2012. It gained popularity as a "legal" alternative to classic cannabis in countries where it was not controlled. The popularity of UR-144 means that this substance is also abused by individuals driving motor vehicles. This article describes a case of driving under the influence (DUI) of UR-144. The aim of the undertaken case analysis and presenting description of pharmacological similarity of THC and UR-144 is to answer the question whether UR-144 can produce effects incompatible with safe driving. METHODS: Blood from the driver was obtained by a physician approximately 2 h after the collision and 4.5 h after self-reported dosing. Police from the crash site provided behavioral observations, and the physician performed medical examination. Blood was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The developed method was described in detail. The method was linear in the range of 0.5-50 ng/mL; the precision and accuracy values obtained were less than 15%. The symptoms observed by police and physician who collected the blood sample were described. RESULTS: In the blood sample collected from the driver, UR-144 and its major pyrolysis product [1-(1-pentyl-1H-indol-3-yl)-3-methyl-2-(propan-2-yl)but-3-en-1-one] were detected. Whole-blood concentration of UR-144 was 14.6 ng/mL. The result of blood analysis and observed symptoms clearly indicated that the driver was under the influence of UR-144. CONCLUSIONS: UR-144 produces effects and impairment similar to or even more dangerous than delta-9-tetrahydrocannabinol (Δ(9)-THC), making it unsafe for driving. Therefore, UR-144 should be treated as a potentially dangerous substance in traffic safety.

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Herbal mixtures contain synthetic cannabinoids, which can cause severe intoxications. Due to the great variety and the changing spectrum of substances on the drug market, prevalence data are limited, and data on prevalence rates of synthetic cannabinoids in forensic cases are not available. The present study was performed to survey the prevalence of synthetic cannabinoids in cases of traffic and criminal offences in the German state Hesse in 2010. The applied analytical method covered all synthetic cannabinoids on the drug market at that time, and with 20% of the blood samples (422 out of 2201) a representative number was reanalyzed. In twelve samples synthetic cannabinoids were identified and a prevalence of 2.8% was estimated. Consumption patterns showed predominantly cases of multi-drug consumption (10 cases); the combination with cannabis or alcohol was frequent (four cases each). The observed deficits were moderate with the exception of aggravation of paranoia in one case. The symptoms were either compatible with the effects of cannabinoid agonists or attributable to alcohol or other drugs found in the blood samples. Our current analytical strategy is to perform such analyses only in cases where use is suspected or where symptoms are not explained by routine toxicological analyses. Hence, the positive rate is rather low highlighting the need to keep up with the developments on the drug market and to establish sensitive screening methods covering a broad range of substances that can be updated fast, e.g., relying on collections of mass spectrometric reference data.

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