Gabapentin in drugged driving investigations.

The increasing use and misuse of gabapentin pose a major risk to public health and traffic safety. Gabapentin has been approved by the Food and Drug Administration (FDA) since 1993 for adjunctive therapy in the treatment of epilepsy and neuralgia but is increasingly being prescribed for numerous off-label uses including insomnia, anxiety, depression, and migraine. Reported side effects include blurred vision, drowsiness, and loss of coordination. Driving behaviors such as exiting the lane of travel and crashes have been reported in connection to drugged driving investigations concerning gabapentin. To further assist with the toxicological interpretation of gabapentin in driving under the influence of drugs (DUID) scenarios, a review of approximately 108,000 gabapentin-positive DUID cases was conducted. Of those, 858 cases met inclusion criteria and underwent additional evaluation. Blood specimens were screened via enzyme-linked immunosorbent assay (ELISA) and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for quantitation of gabapentin. This review found an overall DUID gabapentin positivity of 7.9% between January 2020 and December 2022; 17 states from various geographical regions had at least one positive gabapentin DUID case. Observations in six driving and human performance cases where gabapentin was the only drug reported were consistent with the known adverse effects of the medication. Half of the case histories reviewed involved crashes where the driver was determined to be at fault. Additionally, 94% of the cases in this review involved gabapentin in combination with other drugs. The most prevalent drug combinations were opioids and gabapentin present in 64% of cases.

Increasing prevalence of designer benzodiazepines in impaired driving: A 5-year analysis from 2017 to 2021.

Designer benzodiazepine (DBZD) use has been increasing over the past decade and poses a threat to human health and safety, particularly when involved in driving under the influence of drug (DUID) cases. Over a 5-year period between 2017 and 2021, there were 1,145 reported DBZDs in 805 blood samples submitted from law enforcement agencies for DUID testing. Eleven different DBZDs were detected, including three metabolite pairs: etizolam/alpha-hydroxyetizolam, clonazolam/8-aminoclonazolam, diclazepam/delorazepam, flualprazolam, flubromazolam, flubromazepam, bromazolam and bromazepam. Etizolam/alpha-hydroxyetizolam (n = 485) and flualprazolam (n = 149) were the most frequently detected DBZDs, at 60% and 18%, respectively. Driving behavior, standardized field sobriety test performance and physical observations of individuals suspected of DUIDs, whose blood sample was toxicologically confirmed for one or more DBZDs, were consistent with the effects caused by central nervous system depressants. Each DBZD has its own unique timeline, and toxicology testing had to be frequently updated to reflect the state of the novel psychoactive substance market. DBZDs play a role in impaired driving and can be the sole intoxicant in DUID cases.

Poison hemlock determination in postmortem samples.

Poison hemlock (Conium maculatum L.) is a weed that grows rampant in many areas of North America. Forensic toxicology laboratories rarely receive requests to analyze biological specimens for the presence of poison hemlock. This report discusses two postmortem cases that were encountered over a decade apart and describes different analytical approaches that may be used to quantify coniine, a primary poison hemlock alkaloid, in biological specimens. The first case is from 2004 and involves a 27-year-old female that was found deceased in a relatively isolated area of California. Based on the presence of plant material at the scene and signs of its ingestion at autopsy, the possibility of hemlock poisoning was considered. Toxicological testing of the blood and gastric content by quantitative selected-ion monitoring Gas Chromatography/Mass Spectrometry (SIM-GC/MS) revealed the presence of coniine at concentrations of 410 ng/mL and 9300 ng/mL, respectively. The second case is from Pennsylvania and was sent for analysis in the spring of 2019. In this case, a male in his forties was found deceased in the kitchen area of a camper. Green substances, in liquid and residue forms, were observed in the sink. Mixtures of leaf-like material were also found in several bowls and pans. Subclavian blood screened positive for coniine by full-scan Gas Chromatography/Mass Spectrometry (GC/MS). Semi-quantitative confirmation testing was performed by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and showed the presence of coniine at a concentration of 35 ng/mL. These analytical approaches can be used to substantiate or exclude poison hemlock exposure as a cause of death.

Emergence of Delta-8 Tetrahydrocannabinol in DUID Investigation Casework: Method Development, Validation and Application.

Cannabinoid is the most frequently reported illicit drug class in Driving Under the Influence of Drugs (DUID) investigation casework. In recent years, our laboratory observed an increasing rate of overlapping peaks for the cannabinoid confirmation performed using 2D high-performance liquid chromatography (LC)--tandem mass spectrometry (MS-MS). Starting in early 2018, the incidence of unresolved interfering substances increased, contributing to a higher rate of canceled testing that peaked at 3.7% in February 2019. The observed interference demonstrates a distinctive pattern affecting the identification and quantification of both delta-9 tetrahydrocannabinol (THC) and delta-9 carboxy THC. An improved quantitative method was developed and validated to separate delta-8 and -9 isomers and their metabolites in blood. All acceptance criteria were met, with identical measurement ranges from the original method (lower limit of quantitation: 0.5 ng/mL for delta-9 THC, 1.0 ng/mL for 11-hydroxy delta-9 THC and 5.0 ng/mL for delta-9 carboxy THC). Cannabinoids were extracted from whole blood using liquid-liquid extraction, separated in a 2D LC system over a run time of 10 min and detected by an MS-MS system equipped with ESI source operating in positive ionization mode with scheduled multiple reaction mass spectrometric monitoring. The LC system consisted of a pair of Phenomenex® SecurityGuard™ C6 Phenyl (4 × 2 mm) cartridges for extracting the compounds with 5 mM ammonium formate buffer in deionized (DI) water and 0.1% formic acid in methanol as mobile phase, and a Phenomenex® Kinetex C18 column (100 × 3 mm) with 0.1% formic acid in DI water and 0.1% formic acid in methanol for LC separation at 45°C. Each set of isomers was fully resolved by the longer run-time method. To the authors' knowledge, this is the first report of a method that successfully quantitates these primary cannabinoids in blood specimens where significant concentrations of both delta-9 and delta-8 isomers are present.

11-Year Study of Fentanyl in Driving Under the Influence of Drugs Casework†.

Prior to 2017, heroin and other prescription opioids were the most prevalent opioids implicated in driving under the influence of drugs (DUID) investigation cases, and fentanyl was rarely included in the scope of toxicological analysis. Fentanyl has become the most frequently identified opioid in DUID cases, with many suspected heroin cases turning out to be only fentanyl. A review of fentanyl-positive DUID cases at NMS Labs was performed to provide prevalence information, change in concentration, patterns of combined drug use, indicators of impairment and driving behavior in order to assist with the toxicological interpretation of DUID scenarios involving fentanyl. Fentanyl-positive DUID cases received between January 2010 and December 2020 were examined. Blood results were confirmed and quantitated for fentanyl, norfentanyl and acetylfentanyl using a liquid chromatography--tandem mass spectrometry analysis with a limit of quantitation of 0.10, 0.20 and 0.10 ng/mL, respectively. Of 153,234 blood cases examined for DUID over 11 years, fentanyl was confirmed positive in 6,779 (4.4%) cases. However, there were significant changes in positivity over time. Fentanyl percentage positivity increased from 0.60% in 2010 to 12% in 2020. Of 5,976 confirmed fentanyl-positive cases in 2018-2020, blood concentrations >4.0 ng/mL were observed in 44% (2018), 55% (2019) and 59% (2020) of cases. Polypharmacy was common with 87% of blood samples confirmed positive for fentanyl and at least one other compound. Stimulant was the most commonly identified drug class in cases where at least one additional drug class was present. This study illustrates the importance of including fentanyl in a routine blood DUID panel.

Recommendations for Toxicological Investigation of Drug-Impaired Driving and Motor Vehicle Fatalities-2021 Update.

This report describes updates to the National Safety Council's Alcohol, Drugs and Impairment Division's recommendations for drug testing in driving under the influence of drug (DUID) cases and motor vehicle fatalities. The updates are based on a survey of drug testing practices in laboratories in the USA and Canada, a comprehensive review of the prior recommendations and data and research on drugs most frequently detected in DUID cases. A consensus meeting was held with representative forensic science practitioners and the authors of this report to update recommendations. No changes were made to the Tier I scope; however, there were changes to cutoffs of some analytes for blood, urine and oral fluid. Due to increased prevalence in DUID cases, trazodone and difluoroethane were added to the Tier II scope. For clarification, Tier I cutoffs reflect free concentrations, and hydrolysis is recommended but not required. The consensus panel concluded that urine is an inferior matrix to blood and oral fluid as it may represent historical use or exposure unrelated to observed impairment; therefore, future iterations of these recommendations will not include urine as a recommended matrix. Laboratories currently testing urine should work with traffic safety partners to encourage the use of blood and oral fluid as more appropriate specimens and adjust their capabilities to provide that testing.

The Trouble With Kratom: Analytical and Interpretative Issues Involving Mitragynine.

Mitragynine is the primary active alkaloid in the leaves of the tropical tree Mitragyna speciosa, and goes by the popular names "Kratom", biak-biak and maeng da. Mitragynine is increasingly seen in forensic toxicology casework including driving under the influence of drugs and medicolegal death investigation cases. The toxicity of mitragynine continues to be debated in the scientific community as advocates highlight its long history of use in Southeast Asia and testimonials to its benefits by present-day users, while opponents point to an increasing number of adverse events tied to mitragynine use in Western societies. Quantitative reports of mitragynine in biological specimens from forensic investigations in the literature are sparse and may be influenced by poor analyte stability and inadequate resolution of mitragynine from its diastereomers, which could lead to falsely elevated concentrations and subsequently render those reported concentrations inappropriate for comparison to a reference range. Over the course of 27 months, 1,001 blood specimens submitted to our laboratory tested positive for mitragynine using a sensitive and specific quantitative LC-MS/MS method; concentrations ranged from 5.6-29,000 ng/mL, with mean and median concentrations of 410 ± 1,124 and 130 ng/mL, respectively. Mitragynine presents an analytical challenge that requires a method that appropriately separates and identifies mitragynine itself from its isomers and other related natural products. We describe a validated analytical method and present a short series of case reports that provide examples of apparent adverse events, and the associated range of mitragynine concentrations. This type of analytical specificity is required to appropriately interpret mitragynine concentrations detected in biological specimens from forensic casework and assess its potential toxicity.