Advanced LC-QTOF-MS Analysis Detects Drug Presence in California Traffic Fatalities

A joint study between the University of California (San Francisco and Davis, California campuses) and the Harbor-UCLA Medical Center (Los Angeles, California) reported on the presence of new psychoactive substances (NPS) detected in serum samples from roadway crash victims in northern and southern California in 2024.

Liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was used in the analysis of serum samples taken from 1000 roadway crash victims for what the researchers wrote was the first formal report of multiple NPS and NPS classes quantified in a large survey of roadway crash cases in the United States. A paper based on their work was published in Frontiers in Toxicology (1).

Researching the impact of drugs regarding impaired driving and motor vehicle crashes (MVCs) began in the 1980s (2). A pair of studies performed on drivers killed in their crashes in Los Angeles in 1985 –1986 and 1987–1988 found the presence of drugs in 30% (total sample size of 102) and 12% (total sample size of 492) of the fatalities, respectively (3). A nationwide review of data from the Fatality Analysis Reporting System, a survey of MVCs resulting in at least one death on our country’s public roads, revealed a steady increase in the prevalence of drugs in MVCs (from 18.1% of 6686 crashes in 1999 to 29.1% in 2010), with cocaine and cannabis being the most reported drugs (4,5). Prescription drugs as a broad category, however, were more prevalent than cocaine, cannabis, or other Schedule I drugs; the presence of oxycodone, hydrocodone, and alprazolam have shown significant, steady increases since 1999 (4).

In this study, all patients 18 and older presenting to two urban trauma centers in California within 6 h of a roadway crash who were undergoing a blood draw as part of their routine Emergency Department (ED) care were eligible for inclusion. Patients were excluded if they were not undergoing a blood draw as part of their ED care. If a blood draw was performed without collecting blood for drug and alcohol testing; if the initial blood draw occurred more than 6 h from the time of the crash; or if the patient was in police custody at the time of presentation or was taken into custody during the first 24 h of hospitalization.

Mass spectrometry (MS) was performed using the TOF/MS mode in one run followed by a QTOF/MS run using auto MS/MS data acquisition. An electrospray ionization source in the positive and negative modes was used to ionize analytes in the extract. MS was performed using the TOF/MS mode in one run followed by a QTOF/MS run using auto MS/MS data acquisition. An electrospray ionization source in the positive and negative modes was used to ionize analytes in the extract (1).

Of the aforementioned1000 cases, 290 were positive for at least one traditional recreational drug (TRD) or NPS (29%). Of the 288 that were positive for TRDs, 15 have NPS (4.9%). There were eight unique NPS detected with an overall detection frequency of 26. Only CNS depressants were detected, including designer benzodiazepines, new synthetic opioids, and the plant-derived opioid, mitragynine. Bromazolam (detection frequency, DF = 7) was the most detected, followed by para-fluorofentanyl (DF = 4) and mitragynine (DF = 3). The five other NPS detected includes acetyl fentanyl, N-methyl norfentanyl, protonitazene, etizolam, and xylazine. In one case three NPS were detected, while in six, two NPS were detected.

All but one case also had one or more traditional recreational drugs, of which fentanyl (DF = 9), methamphetamine (DF = 9), and delta-9-THC (DF = 4) were the most detected. Cocaine was detected in two cases while the inactive cocaine metabolite, benzoylecgonine, was detected in three cases. In nine cases, the precursor for fentanyl, ANPP, was detected. Two adulterants, quinine and lidocaine, were detected in two and three cases, respectively. The impurity obtained during methamphetamine synthesis, N,N-dimethylamphetamine, was detected in one case. Sixteen of the seventeen cases tested negative for ethanol (1).

The researchers state that, although the number of cases where NPS were found in their cohort is limited, the findings from their study provide additional evidence that NPS poses an ongoing danger to road safety, as well as emphasize the need for changes in policy to expand the NPS testing infrastructure. They believe that future research should remain focused on detecting these substances in roadway accidents, with emphasis on the drivers of the vehicles in question, as they are the element most responsible for injuries and fatalities in crashes. Furthermore, the development of a dynamic roadside testing strategy adaptable to detecting those drivers impaired by NPS in close to, if not in, real-time would be, in their opinion, most beneficial (1).

References

1. Gerona, R.; Tomer, D.; Nielsen, D, et al. New Psychoactive substances in Roadway Crash Victims in California. Front. Toxicol. 2025, 7, 1572324. DOI: DOI: 10.3389/ftox.2025.1572324
2. Williams, A. F.; Peat, M.A.; Crouch, D. J. et al.. Drugs in Fatally Injured Young Male Drivers. Public Health Rep. 1985, 100 (1), 19-25.
3. Budd, R. D.; Muto, J. J.; Wong, J. K. Drugs of Abuse Found in Fatally Injured Drivers in Los Angeles County. Drug Alcohol Depend. 1989, 23 (2), 153-158. DOI: 10.1016/0376-8716(89)90021-5
4. Rudisill, T. M.; Zhao, S.; Abate, M. A. et al. Trends in Drug Use Among Drivers Killed in U.S. Traffic Crashes, 1999-2010. Accid. Anal Prev. 2014, 70, 178-87. DOI: 10.1016/j.aap.2014.04.003
5. Brady, J. E.; Li, G. Trends in Alcohol and Other Drugs Detected in Fatally Injured Drivers in the United States, 1999-2010. Am. J. Epidemiol. 2014, 179 (6), 692-9. DOI: 10.1093/aje/kwt327