Search

Abstract Background According to the World Health Organization, road traffic injuries lead to 1.3 million deaths each year and represent the leading cause of death for young adults under 30 years old. The use of psychoactive substances, including alcohol, drugs and pharmaceuticals, is a well-known risk factor for road traffic injuries. Our study aims to assess the prevalence of substances consumed by drivers in western Switzerland. Such studies are pivotal to improving prevention and developing public awareness campaigns. Methods To assess the prevalence of psychoactive substances among drivers, roadside controls were performed in collaboration with local police, using their classical sampling procedures to detect drivers under the influence of drugs or alcohol over two time periods (P1: 2006-2008, P2: 2017-2020). When impaired driving was not suspected by the police, minimally invasive sampling strategies (i.e., oral fluids during P1 and dried blood spots during P2) were performed on volunteer drivers after a road safety survey. A posteriori analyses and statistical interpretation were then performed. Results Among the 1605 drivers included in the study, 1048 volunteers provided an oral fluid sample, while 299 provided a dried blood spot sample. The percentage of drivers testing positive for at least one substance that can impact driving abilities was stable over time, with a rate of 10.5% positivity measured over both periods. Considering the different categories of substances, a slight variation was observed between both periods, with 7.6 and 6.3% of pharmaceuticals and 3.6 and 4.9% of illicit drugs for P1 and P2, respectively. Regarding the consumption of illicit drugs, the highest percentage of positivity was measured in biological fluids of drivers under the age of 35, during nights and week-ends, periods which are considered particularly prone to fatal accidents for this age group. Disturbingly, the road safety survey highlighted that drivers’ perception of the risk of getting positively controlled while driving after drug consumption is low (3.3 on a 1-to-10 scale, N = 299). Conclusion The number of positive cases measured in voluntary drivers who passed the preliminary police check demonstrates the importance of systematic biofluid sampling strategies regarding driving under the influence of psychoactive substances. Although the number of fatal road accidents globally has decreased over time, the results of this study reveal the need for both better prevention and deterrent processes that could potentially reduce the risk of fatal road accidents associated with drug consumption.

Abstract Diagnostics of myocardial infarction in human post-mortem hearts can be achieved only if ischemia persisted for at least 6–12 h when certain morphological changes appear in myocardium. The initial 4 h of ischemia is difficult to diagnose due to lack of a standardized method. Developing a panel of molecular tissue markers is a promising approach and can be accelerated by characterization of molecular changes. This study is the first untargeted metabolomic profiling of ischemic myocardium during the initial 4 h directly from tissue section. Ischemic hearts from an ex-vivo Langendorff model were analysed using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) at 15 min, 30 min, 1 h, 2 h, and 4 h. Region-specific molecular changes were identified even in absence of evident histological lesions and were segregated by unsupervised cluster analysis. Significantly differentially expressed features were detected by multivariate analysis starting at 15 min while their number increased with prolonged ischemia. The biggest significant increase at 15 min was observed for m/z 682.1294 (likely corresponding to S-NADHX—a damage product of nicotinamide adenine dinucleotide (NADH)). Based on the previously reported role of NAD+/NADH ratio in regulating localization of the sodium channel (Nav1.5) at the plasma membrane, Nav1.5 was evaluated by immunofluorescence. As expected, a fainter signal was observed at the plasma membrane in the predicted ischemic region starting 30 min of ischemia and the change became the most pronounced by 4 h. Metabolomic changes occur early during ischemia, can assist in identifying markers for post-mortem diagnostics and improve understanding of molecular mechanisms.

Driving under the influence of psychoactive substances is a major cause of motor vehicle crashes. The identification and quantification of substances most frequently involved in impaired-driving cases in a single analytic procedure could be an important asset in forensic toxicology. In this study, a highly sensitive and selective liquid chromatography (LC) approach hyphenated with Orbitrap high-resolution mass spectrometry (HRMS) was developed for the quantification of the main drugs present in the context of driving under the influence of drugs (DUID) using 100 μL of whole blood. This procedure involves a simple sample preparation and benefit from the selectivity brought by parallel reaction monitoring (PRM) allowing to solve most DUID cases using a single multi-analyte injection. The method was fully validated for the quantification of the major classes of psychoactive substances associated with impaired-driving (cannabinoids, cocaine and its metabolites, amphetamines, opiates and opioids, and the major benzodiazepines and z-drugs). The validation guidelines set by the “Société Française des Sciences et des Techniques Pharmaceutiques” (SFSTP) were respected for 22 psychoactive substances using 15 internal standards. Trueness was measured to be between 95.3 and 107.6% for all the tested concentrations. Precision represented by repeatability and intermediate precision was lower than 12% while recovery (RE) and matrix effect (ME) ranged from 49 to 105% and from −51 to 3%, respectively. The validated procedure provides an efficient approach for the simultaneous and simple quantification of the major drugs associated with impaired driving benefiting from the selectivity of PRM.

Illicit drugs are a global health problem, since both their acute and chronic consumption have negative impacts on the drug user's health. Drug checking facilities are receiving growing interest as they allow drug users to chemically analyze their product prior to consumption to assess the presence of adulterants or other non-expected substances. Such harm reduction programs allow the reduction of the risks associated with drug consumption without encouraging it. In particular, the emergence of new psychoactive substances (NPS) emphasizes the risk for the population increasing the diversity and the lability of illicit drugs on the market. Analytical developments are required to catch up with this rapid evolution and reduce the potential harm caused by such consumption. In this study, we developed a matrix-assisted laser desorption/ionization (MALDI) high-resolution mass spectrometry (HRMS) strategy for the high-throughput qualitative and quantitative analysis of drug checking samples. The use of online-based m/z cloud library for untargeted compound search improved the ability to identify unknown compounds. Sixty-seven drug checking samples were analyzed using this analytical strategy, allowing the detection of 10 designer drugs and several classical drugs of abuse (mainly cocaine and MDMA) as well as adulterants and contaminants. The results were then compared with routine analyses of the same samples using conventional approaches showing similar performance while removing the use of chromatographic separation thus resulting in a significant reduction of the time required for sample preparation and analysis. This study enlightens the potential of MALDI-HRMS as a high-throughput approach allowing to speed-up up to six times the identification and quantification of substances enabling to catch the fast changes on the drug of abuse market. This strategy could be an interesting alternative analytical approach, allowing better prevention and harm reduction for drug users.