Heather M. Barkholtz

Pharmacokinetic (PK) studies require temporally precise measurements of drug concentrations in biological matrices, most commonly whole blood or plasma. However, repeated venous sampling may increase participant burden and complicate PK‐intensive study designs. Needle‐free blood collection devices that access peripheral intravenous (IV) catheters may provide an alternative approach to repeated venipuncture while maintaining sampling schedules and specimen quality. This pilot study evaluated the feasibility of integrating the PIVO Pro needle‐free blood collection device into a PK‐intensive human laboratory study of inhaled Δ ⁸ ‐tetrahydrocannabinol (Δ ⁸ ‐THC), Δ ⁹ ‐THC, and placebo. Participants completed a screening visit and three dosing visits conducted in a university research facility equipped with a full‐scale driving simulator. During each dosing visit, venous blood samples were collected at nine time points over approximately 8 h through an indwelling peripheral IV catheter using the PIVO device. All participants reported that study procedures, including blood collection, were acceptable. Approximately 40% of vascular access sites required replacement, most commonly within the first hour and typically associated with poor initial blood return. Despite slower flow compared with standard venipuncture, sampling was generally sufficient to maintain the PK sampling schedule. One mild adverse event related to vascular access (localized bruising) was observed. These findings demonstrate the operational feasibility of needle‐free blood collection through indwelling IV catheters in a PK‐intensive research protocol conducted outside a traditional clinical research unit. Further studies are warranted to compare analytical performance and access durability relative to conventional venous sampling approaches.

The increasing prevalence of opioid misuse, particularly the adulteration of illicit substances with fentanyl, has heightened the need for effective field detection methods for unknown powders. First responders, including chemical emergency response and Hazardous Materials (HazMat) teams, face significant challenges in assessing chemical threats in real-time without the resources of a controlled laboratory environment. Immunoassay test strips are commonly used for drug detection and are considered potential tools for identifying fentanyl in emergency scenarios. However, the impact of common diluents (substances such as sugar, flour, and other commonplace additives) on the accuracy of these test strips is unexplored. This study evaluates the limit of detection (LOD) of a popular commercially available fentanyl test strip (FTS) in the presence of various diluents commonly found in emergency situations. The experimental LOD was determined to be 0.05 μg/mL, significantly lower than the reported LOD of 0.20 μg/mL. While no false positives were observed with diluents alone, the presence of diluents in fentanyl solutions altered FTS results, requiring higher concentrations of fentanyl to achieve a positive reading. Results were often difficult to interpret, particularly near the LOD, which could pose challenges for first responders in real-world scenarios. This work is the first to assess the application of FTS to chemical emergency response situations and threat assessment of unknown powders. Commercially available FTS are cost-effective, user-friendly, provide rapid results, and detect low concentrations of fentanyl even in the presence of other substances.

Objective: Nonfatal overdoses provide critical insights into the substance use crisis, offering opportunities for timely interventions and prevention. This study pilots a nonfatal overdose biosurveillance strategy to analyze the demographic, clinical, and toxicological profiles of overdose patients, aiming to identify patterns and risk factors associated with these incidents. Methods: We assessed residual urine specimens collected from emergency department patients experiencing a nonfatal overdose at 2 hospitals in Wisconsin from August 2022 through February 2024. We collected data on patient demographic characteristics, results of clinical toxicology screening, manner of overdose, risk factors for overdose, and discharge status. Statistical analyses identified associations and odds ratios (ORs) among patient characteristics, detected drugs, and discharge status. Results: Of the 79 patients in the study, many had risk factors for overdose, including substance use disorder (48%), history of a mental health condition (43%), and polysubstance use (72%). Synthetic opioids had a strong positive association with a history of overdose (OR = 3.86). The presence of stimulants and antidepressants showed moderate sex-based associations, while race was linked to differing discharge status. Polysubstance use had a positive association with some drug combinations, such as narcotic analgesics and cocaine (OR = 4.00). Conclusions: This study highlights the prevalence of polysubstance use and identifies key demographic and clinical factors associated with nonfatal overdoses. These findings underscore the need for comprehensive, real-time biosurveillance to inform targeted public health interventions and improve patient outcomes. Enhanced understanding of these patterns can lead to more effective strategies for overdose prevention and management, addressing a critical gap in current public health approaches.

Forensic and clinical laboratories are expected to provide a rapid screening of samples for a wide range of analytes; however, the ever-changing landscape of illicit substances makes analysis complicated. There is a great need for untargeted methods that can aid these laboratories in broad-scope drug screening. Liquid chromatography hyphenated with high-resolution mass spectrometry (LC-HRMS) has become a popular technique for untargeted screening and presumptive identification of drugs of abuse due to its superior sensitivity and detection capabilities in complex matrices. An untargeted extraction and data acquisition method was evaluated for the broad screening of high-priority drugs of abuse in whole blood. A total of 35 forensically relevant target analytes were identified and extracted at biologically relevant low and high (10× low) concentrations from whole blood using supported liquid extraction. Data-independent acquisition was accomplished using ultraperformance liquid chromatography and a quadrupole time-of-flight mass spectrometry. Results were acceptable for screening assays, with limits of detection at or below the recommended low-concentration cutoffs for most analytes. Analyte ionization varied from 30.1 to 267.6% (average: 110.5%) at low concentrations and from 8.6 to 383.5% (average: 93.6%) at high concentrations. Extraction recovery ranged from 8.5 to 330.5% (average: 105.3%) at low concentrations and from 9.4 to 127.5% (average: 82.7%) at high concentrations. This variability was also captured as precision, ranging from 4.7 to 135.2% (average: 36.5%) at low concentrations and from 0.9 to 59.0% (average: 21.7%) at high concentrations. The method described in this work is efficient and effective for qualitative forensic toxicology screening, as demonstrated by analysis of 166 authentic suspected impaired driver and postmortem specimens. That said, it is critical that laboratories establishing untargeted LC-HRMS screening assays be aware of the strengths and limitations across diverse drug categories and chemical structures.

Little is known about the demographics of people who use cannabis, including how use trends within population subgroups have evolved over time. It is therefore challenging to know if the demographics of participants enrolled in cannabis clinical trials are representative of those who use cannabis. To fill this knowledge gap, data from the National Survey on Drug Use and Health (NSDUH) on “past-month” cannabis use across various population subgroups in the United States was examined from 2002 to 2021. The most notable increases in “past-month” cannabis use prevalence occurred in those aged 65 and older (2,066.1%) and 50–64-year-olds (472.4%). In 2021, people reporting “past-month” cannabis use were 56.6% male and 43.4% female. Distribution across self-reported race and ethnicity was 64.1% White, 14.3% Black, 14.1% Hispanic, and 3.1% more than one race. And many ages were represented as 24.4% were 26–34, 24.1% were 35–49, 22.4% were 18–25, and 17.6% were 50–64 years old. To understand if these population subgroups are represented in cannabis clinical trials, participant demographics were extracted from peer-reviewed clinical trials reporting on pharmacokinetic and/or pharmacodynamic models of cannabis or cannabinoids. Literature was grouped by publication year (2000–2014 and 2015–2022) and participant prior exposure to cannabis. Results identified that cannabis clinical trial participants are skewed toward overrepresentation by White males in their 20s and 30s. This represents structural discrimination in the research landscape that perpetuates social and health inequities.

Methamphetamine exists as two stereoisomers: S-(+)-methamphetamine ((+)-MAMP) and R-(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central nervous system stimulant, available as a pharmaceutical and clandestine drug of abuse. However, the (-)-MAMP stereoisomer is less well understood despite commercial availability for over 30 years as an over-the-counter (OTC) nasal decongestant in the Vicks Vapor Inhaler (a product of Procter & Gamble). Recently, several generic versions have become available, decreasing the cost and increasing the availability of (-)-MAMP-containing nasal sprays to consumers. Despite widespread commercial availability and use in the United States, a paucity of literature exists on the pharmacology of (-)-MAMP in humans. This knowledge gap is problematic, given the difficulty in separating (-)-MAMP and (+)-MAMP isomers in laboratory assays for workplace drug testing, suspected impaired drivers, post-mortem investigations, and assessment of drug involvement in crimes. In response, this systematic review of the literature coalesces and summarizes available knowledge of (-)-MAMP pharmacology in humans. It was found that available knowledge relies heavily on urine drug and metabolite concentrations, systematic pharmacokinetics studies are lacking, and existing knowledge has been derived from a total of 99 unique participants. The impacts of highlighted gaps in the literature are discussed, focusing on forensic toxicology and law enforcement, and future research directions are suggested.

Forensic science is a broad and rapidly developing field where fundamental scientific principles and techniques are used to investigate crimes. As the field evolves, universities offering forensic science degrees are increasing in both number and diversity of curricula. Paramount to any discussion around forensic science education is an assessment of what educational degrees are preferred by those hiring both entry- and supervisory-level forensic scientists. Quantification of degree preference through surveys of hiring officials occurred in 1986 and 1996. Since then, the Forensic Science Education Programs Accreditation Commission was established and has flourished, potentially enhancing the desirability of forensic science degrees. An updated survey was conducted to identify current educational background preferences within the field. The survey was distributed to members of the American Society of Crime Laboratory Directors and members of the Society of Forensic Toxicologists in hiring or leadership roles, yielding 221 responses. Results indicated a continued preference for a degree combination of master’s in forensic science and a bachelor’s degree in physical or biological sciences for both entry- and supervisory-level candidates. Holding only a bachelor’s in the physical or biological sciences was also preferred for entry-level candidates whereas the preference for supervisory-level candidates was strongly influenced by the respondents’ terminal degree.

Drug-impaired driver detection is a critical element of traffic safety. However, shifting drug use patterns over time and geography may limit the long-term reliability of assay-based screening tools. In this work, we compare qualitative results from the Abbott SoToxa^® oral fluid (OF) screening device to Quantisal™ OF and whole blood. Our objective was to examine these three qualitative toxicological approaches, scope applicability of OF collection at the roadside, and compare them with a previous analysis of SoToxa^® in Wisconsin. OF specimens were screened with the SoToxa^® for six drugs or drug classes including amphetamine, benzodiazepines, cocaine, methamphetamine, opioids and tetrahydrocannabinol (THC). OF and blood specimens were collected from 106 participants. Quantisal™ OF and blood specimens were screened for drugs on ultra-performance liquid chromatography coupled to quadrupole time-of-flight high-resolution mass spectrometry (UPLC–QToF-HRMS) using a data-independent acquisition mode. UPLC–QToF-HRMS data were compared to comprehensive spectral libraries, and drugs were qualitatively identified. Drug Recognition Expert evaluations were performed, and face sheets submitted for 21 participants in this work. In general, the SoToxa^® results were consistent with the combined qualitative results observed in Quantisal™ OF specimens and whole blood specimens. Limitations were uncovered for benzodiazepines, opioids and THC. The SoToxa^® benzodiazepine assay has high cutoff concentrations for diazepam and clonazepam, limiting its sensitivity and positive predictive value when considering these drugs. SoToxa^® opioid screening did not detect fentanyl, which is increasingly prevalent among drug users. Finally, ∆⁹-THC and its major metabolite 11-nor-9-carboxy-∆⁹-THC are lipophilic, limiting partitioning into OF. Despite these limitations, the SoToxa^® instrument may be useful in assisting law enforcement with identifying individuals driving under the influence of drugs and establishing probable cause at roadside for making impaired driving arrests. Furthermore, Quantisal™ OF may be useful as screening specimens due to their ease of collection and results consistent with whole blood.

In this work, 114 volunteers were dosed with 80-proof liquor to produce peak blood-alcohol concentration (BAC) or breath-alcohol concentration (BrAC) of 0.040–0.080 g/100 mL blood or g/210 L breath. This was followed by a 30 minute deprivation period before simultaneous blood and breath samples were collected and the alcohol concentration quantified. BAC was determined by gas chromatography with flame ionization detection and BrAC by a dual-sensor Intox EC/IR II instrument. Paired Student t-tests showed that differences between paired blood- and breath-alcohol results differed significantly. Results from these two measurement methods are highly correlated and, on average, measured BAC was 11.3% greater than BrAC. There were 10 instances of BrAC being greater than the corresponding BAC, and the average difference between these two values was 0.0059 g/100 mL. Agreement plots of coupled BAC and BrAC revealed a mean bias of 0.00754 g/100 mL and 95% limits of agreement (LOA) at −0.00705 and 0.0221 g/100 mL. Once BrAC values were truncated to the hundredths place as required by Wisconsin state statute, only three participants had greater BrAC than corresponding BAC, with an average difference between these values of 0.008 g/100 mL. Agreement plots with truncated BrAC values gave a mean bias of 0.0120 g/100 mL and 95% LOA at −0.00344 and 0.0275 g/100 mL. Data showed that typically, blood samples had greater alcohol concentrations than corresponding breath values. Differences were exacerbated by Wisconsin’s statutory requirement that reported breath alcohol measurements be truncated to the hundredths place, whereas blood has no corresponding mandate.