Driving Under the Influence of Drugs: A Single Parallel Monitoring-Based Quantification Approach on Whole Blood

Abstract

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.

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

“…Due to the advances in HRMS technology, the new generations of TOF and Orbitrap instruments have the performance characteristics required for reliable and routine quantification, i.e . sensitivity, dynamic range, accuracy, precision, and reproducibility 57–59 . On top of this, HRMS quantification using targeted approaches has additional advantages over QqQ quantification.…”

“…sensitivity, dynamic range, accuracy, precision, and reproducibility. [57][58][59] On top of this, HRMS quantification using targeted approaches has additional advantages over QqQ quantification. One advantage stems from the greater selectivity of HRMS, where with a better separation of ions from interferences, there is a decreased chance of detecting false positives or generating artefactually greater measurements.…”

“…One advantage stems from the greater selectivity of HRMS, where with a better separation of ions from interferences, there is a decreased chance of detecting false positives or generating artefactually greater measurements. Another advantage, which has been discussed previously, is the ability to perform the quantification in full‐scan mode, which means data can be captured for all ions in a sample, giving a global picture that is more representative of the sample 57–60 . This large, global data set allows retrospective analysis and different kinds of post hoc targeted or untargeted data treatments 59 .…”

Survey and Synthesis of State of the Art in Driver Monitoring

“…If this BAC is above the legally authorized value, the results can, if desired, be confirmed by a blood test. With just 100 microliter (µL) of collected blood, one can not only measure the BAC precisely, but also identify and quantify 37 substances that are of interest in the context of drug-impaired driving [234]. Many people, however, drive under the influence without necessarily being stopped and checked by police every time they do so.…”

Survey and synthesis of state of the art in driver monitoring

“…If this BAC is above the legally authorized value, the results can, if desired, be confirmed by a blood test. With just 100 microliter (µL) of collected blood, one can, not only measure the BAC precisely, but also identify and quantify 37 substances that are of interest in the context of drug-impaired driving (92). Many people, however, drive under the influence without necessarily being stopped and checked by police every time they do so.…”