Peer perspectives on friendships among peers with and without intellectual and developmental disabilities: A pilot mixed methods study.

BACKGROUND: The benefits of friendships among peers with and without intellectual and developmental disabilities are well supported by research. However, little is known about the nature of these inclusive friendships in inclusive college courses. METHOD: We explored the perspectives of peers on the development of authentic friendships among peers with and without intellectual and developmental disabilities in inclusive college courses in the United States. We used a sequential, explanatory, transformative mixed methods-grounded theory research design. We integrated quantitative (N = 44) and qualitative (N = 8) findings using blended analysis to inform a preliminary grounded theory of inclusive and reciprocal friendships. RESULTS: Quantitative findings suggest two relationships and one predictor of peers' perceived social engagement. Qualitative findings resulted in five themes that promote friendships. CONCLUSIONS: We propose that the context for developing inclusive friendships could be fostered using the preparation and actions stages of the grounded theory model.

Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is a relatively common inborn error of metabolism, but due to difficulty in accurately predicting affected status through newborn screening, molecular confirmation of the causative variants by sequencing of the ACADVL gene is necessary. Although the ACMG/AMP guidelines have helped standardize variant classification, ACADVL variant classification remains disparate due to a phenotype that can be nonspecific, the possibility of variants that produce late-onset disease, and relatively high carrier frequency, amongst other challenges. Therefore, an ACADVL-specific variant curation expert panel (VCEP) was created to facilitate the specification of the ACMG/AMP guidelines for VLCADD. We expect these guidelines to help streamline, increase concordance, and expedite the classification of ACADVL variants.

N,N-Dimethylpentylone (dipentylone)-A new synthetic cathinone identified in a postmortem forensic toxicology case series.

Synthetic cathinones emerged on the novel psychoactive substance (NPS) drug market as alternatives to controlled stimulants and entactogens such as methamphetamine and 3,4-methylenedioxymethamphetamine. The majority of synthetic cathinones can be subclassified into two groups: beta-keto amphetamines (i.e., NPS with the suffix "drone") and beta-keto methylenedioxyamphetamines (i.e., NPS with the suffix "lone"). Although a significant number of beta-keto amphetamines have been identified, beta-keto methylenedioxyamphetamines have dominated the NPS market, including notable drugs like methylone, butylone, N-ethyl pentylone (ephylone), eutylone and now N,N-dimethylpentylone. N,N-Dimethylpentylone, also known as dipentylone or beta-keto-dimethylbenzodioxolylpentanamine, emerged into the illicit drug supply <2 months of the international control of eutylone (September 2021). A novel standard addition method was developed and validated for N,N-dimethylpentylone, pentylone and eutylone, and 18 postmortem cases were quantitated using the method described in this manuscript. The resulting blood concentration range for N,N-dimethylpentylone in this case series was 3.3 to 970 ng/mL (median: 145 ng/mL, mean: 277 ± 283 ng/mL). Pentylone, a metabolite of N,N-dimethylpentylone, was detected in all cases (range: 1.3-420 ng/mL, median: 31 ng/mL and mean: 88 ± 127 ng/mL). Due to the rise in identifications of N,N-dimethylpentylone in postmortem investigations as well as the potential misidentification of N,N-dimethylpentylone as N-ethyl pentylone, samples testing positive for pentylone should be additionally confirmed for the presence of N,N-dimethylpentylone. Based on prior trends of new synthetic cathinones, it can be theorized that N,N-dimethylpentylone may predominate the US synthetic stimulant market for the next 1-2 years; however, given the emergence of additional closely related isomeric compounds, it is important to utilize methodology capable of differentiating N,N-dimethylpentylone from its isomers (N-isopropylbutylone, N-ethyl pentylone, N-ethyl N-methyl butylone, hexylone, N-propylbutylone, diethylone and tertylone).

Effects of Implementing an Acuity Tool on a Psychiatric Intensive Care Unit.

BACKGROUND: Staff shortages, reduced budgets, and high acuity of violent psychiatric patients can create challenges in psychiatric intensive care units (PICUs). LOCAL PROBLEM: Staffing of the psychiatric unit was based on patient census rather than evidence-based practices. METHODS: A pre-/postintervention design was used to examine changes in nursing satisfaction and patient outcomes as measured with the National Database of Nursing Quality Indicators (NDNQI) survey results. INTERVENTIONS: A psychiatric specific acuity tool was implemented on the PICU of a Veterans Administration hospital. RESULTS: After an initial decrease related to the COVID-19 pandemic, total acuity and the total number of nurses remained relatively stable while the unit census declined. NDNQI survey results improved with the largest being a 52-percentile increase for the quality-of-care summary measure. CONCLUSIONS: An acuity tool can help standardize practice, determine fair patient assignments among staff, increase nurse satisfaction, and promote best practices for patient safety.

Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017-2020: A Review.

An important role of modern forensic and clinical toxicologists is to monitor the adverse events of novel psychoactive substances (NPS). Following a prior review from 2013 to 2016, this critical literature review analyzes and evaluates published case reports for NPS from January 2017 through December 2020. The primary objective of this study is to assist in the assessment and interpretation of these cases as well as provide references for confirmation methods. Chemistry, pharmacology, adverse events and user profiles (e.g., polypharmacy) for NPS are provided including case history, clinical symptoms, autopsy findings and analytical results. Literature reviews were performed in PubMed and Google Scholar for publications using search terms such as NPS specific names, general terms (e.g., 'designer drugs' and 'novel psychoactive substances'), drug classes (e.g., 'designer stimulants') and outcome-based terms (e.g., 'overdose' and 'death'). Government and website drug surveillance databases and abstracts published by professional forensic science organizations were also searched. Toxicological data and detailed case information were extracted, tabulated, analyzed and organized by drug category. Case reports included overdose fatalities (378 cases), clinical treatment and hospitalization (771 cases) and driving under the influence of drugs (170 cases) for a total of 1,319 cases providing details of adverse events associated with NPS. Confirmed adverse events with associated toxidromes of more than 60 NPS were reported including synthetic cannabinoid, NPS stimulant, NPS hallucinogen, NPS benzodiazepine and NPS opioid cases. Fifty of these NPS were reported for the first time in January 2017 through December 2020 as compared to the previous 4 years surveyed. This study provides insight and context of case findings described in the literature and in digital government surveillance databases and websites during a recent 4-year period. This review will increase the awareness of adverse events associated with NPS use to better characterize international emerging drug threats.

Toxicological and pharmacological characterization of novel cinnamylpiperazine synthetic opioids in humans and in vitro including 2-methyl AP-237 and AP-238.

The recent scheduling actions of fentanyl-related substances in both the United States and China have sparked the emergence and proliferation of other generations of "legal" opioids that are structurally distinct from fentanyl, including the recently emerged class of cinnamylpiperazines. In contrast to fentanyl, which contains a piperidine core and a phenethyl moiety, the primary structural components of cinnamylpiperazines are the piperazine core and a cinnamyl moiety. This manuscript reports on the toxicological profile for antemortem and postmortem cases where a cinnamylpiperazine was detected. Samples were quantitatively confirmed using liquid chromatography tandem mass spectrometry. The cases were received between February 2020 and April 2021. Concentrations of 2-methyl AP-237 from four postmortem cases ranged from 820 to 5800 ng/mL, and concentrations of AP-238 from two postmortem cases were 87 and 120 ng/mL. µ-Opioid receptor (MOR) activation potential for 2-methyl AP-237, AP-237, para-methyl AP-237, and AP-238 were studied using a ßarr2 recruitment assay. Efficacies (Emax, relative to hydromorphone) and potencies (EC50) were derived and of the compounds tested AP-238 was the most potent compound in the panel with an EC50 of 248 nM. 2-Methyl AP-237 was found to be the most efficacious drug (Emax = 125%) of the tested cinnamylpiperazines; however, it had substantially less efficacy than fentanyl. The in vitro MOR activation potential of the studied cinnamylpiperazines was lower than that of fentanyl and other novel synthetic opioids (NSOs), in line with the relatively higher concentrations observed in postmortem toxicology samples-an important observational link between in vitro pharmacology and in vivo toxicology.

Analysis of the Illicit Opioid U-48800 and Related Compounds by LC-MS-MS and Case Series of Fatalities Involving U-48800.

We report a method for the detection and quantitation of 12 drugs and 2 metabolites in the same structural class as the illicit mu-opioid agonist U-47700 in human whole blood. These substances are either known or suspected to be present as potential novel opioids in illicit drug markets. The general class of these drugs was developed in pharmaceutical research programs in the 1970s, but these drugs have recently become of concern for overdoses and death in opioid users in the USA and internationally. The scope of analysis included the following compounds: methylenedioxy U-47700, ethylenedioxy U-47700, ethylenedioxy U-51754, U-69593, U-47931E (bromadoline), U-47700, U-48800, U-49900, U-51754, U-50488, propyl U-47700 and isopropyl U-47700. Additionally, two metabolites N,N-didesmethyl U-47700 and desmethyl U-47700 were also included in the scope. Drugs were extracted from human whole blood using solid-phase extraction, and the extracts were analyzed by liquid chromatography--tandem mass spectrometry. The assay was validated with respect to bias, carryover, interference, within-run and between-run precision, and accuracy. Eight medicolegal death investigation cases that had screened positive for U-48800 by liquid chromatography--time-of-flight mass spectrometry were successfully confirmed and quantified using this method. The mean and median concentrations of U-48800 in these cases were 2.5 (±2.1) and 1.8 ng/mL, respectively, with a range of concentrations of 0.27-6.2 ng/mL. Case history information including the presence of other drugs in combination are described and discussed.

Sentanyl: a comparison of blood fentanyl concentrations and naloxone dosing after non-fatal overdose.

INTRODUCTION: Non-pharmaceutical fentanyl and its analogs have driven striking increases in opioid-associated overdose deaths. These highly potent opioids can be found at low concentrations in biological specimens. Little is known regarding the concentrations of these substances among survivors of non-fatal overdoses. In a locale where fentanyl is responsible for the majority of non-fatal opioid overdoses, we compared the concentration of fentanyl in blood to naloxone dosing in the presence and absence of a concurrent sedative-hypnotic exposure. METHODS: In this pilot study, we enrolled adult patients presenting to the emergency department (ED) who: (1) arrived after an overdose requiring naloxone for the reversal of respiratory depression; and (2) who required venipuncture or intravenous access as part of their clinical care. Blood specimens (n = 20) underwent comprehensive toxicology testing, including the quantitation of fentanyl, fentanyl analogs, and naloxone, as well as the detection of common sedative-hypnotics and a wide range of other illicit and pharmaceutical substances. We then compared fentanyl concentrations to naloxone dosing in participants with and without a concomitant sedative-hypnotic exposure. RESULTS: Nineteen of twenty participants (95%) were exposed to fentanyl prior to their overdose; the remaining participant tested positive for heroin metabolites. No participants reported pharmaceutical fentanyl use. Fentanyl analogs - acetylfentanyl or carfentanil - were present in three specimens. In 11 cases, fentanyl and its metabolites were the only opioids identified. Among the fentanyl-exposed, blood concentrations ranged from <0.1-19 ng/mL with a mean of 6.2 ng/mL and a median of 3.6 ng/mL. There was no relationship between fentanyl concentration and naloxone dose administered for reversal. We detected sedative-hypnotics (including benzodiazepines, muscle relaxants, and antidepressants) in nine participants. Among the sedative-hypnotic exposed, fentanyl concentrations were lower, but naloxone dosing was similar to those without a concomitant exposure. CONCLUSIONS: In this study, we found that: 1) fentanyl was present in the blood of nearly all participants; 2) fentanyl concentrations were lower among study participants with concomitant sedative-hypnotic exposure; and 3) the dose of naloxone administered for overdose reversal was not associated with the measured fentanyl concentration in blood specimens. Our results underscore the role that tolerance and concomitant drug exposure play in the precipitation and resuscitation of management of opioid overdose.

A Case of Unintentional Opioid (U-47700) Overdose in a Young Adult After Counterfeit Xanax Use.

ABSTRACT: We report the case of a young adult who became unresponsive after insufflating what he believed to be "crushed Xanax." Naloxone was administered, reversing his altered mental status and respiratory depression. Clinicians suspected opioid toxicity; however, the patient adamantly denied opioid use. Because of unclear etiology of his symptoms, blood and urine specimens were obtained. A urine specimen was split and then submitted for a clinical comprehensive drug screen using gas chromatography-mass spectrometry. The blood specimen and the remaining urine specimen were sent to a reference laboratory for analysis using liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography tandem mass spectrometry. The standard, clinical gas chromatography-mass spectrometry urine drug testing procedure only detected caffeine; however, analysis by liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography tandem mass spectrometry confirmed the presence of U-47700 (a high-potency clandestine opioid) and its metabolites in the urine and blood. These findings implicate U-47700 as the agent responsible for the patient's signs of opioid toxicity. In this case, a young adult intending to use alprazolam encountered U-47700 with life-threatening effect. Clinicians must remain vigilant for symptoms consistent with opioid overdose, especially with increasing prevalence of counterfeit drugs containing clandestine opioids. Clinicians must also consider obtaining specimens for appropriate analytical testing to improve surveillance and facilitate public health interventions.

Evaluating Trends in Novel Psychoactive Substances Using a Sentinel Population of Electronic Dance Music Festival Attendees.

Electronic dance music (EDM) festivals have become a popular venue for recreational drug use, including the use of traditional stimulants like 3,4-methylenendioxymethamphetamine (MDMA) and novel psychoactive substances (NPS). Using this cohort of people who use drugs recreationally, this study sought to collect biological specimens and self-reported drug use data from EDM festival attendees in the United States to monitor regional and temporal trends related to NPS use and turnover between 2014 and 2017. Oral fluid samples were collected at three United States EDM festival locations, including Miami, Florida (2014 to 2017); Tampa, Florida (2017) and Atlanta, Georgia (2017). Samples were screened by liquid chromatography-quadrupole time-of-flight mass spectrometry and confirmed by liquid chromatography-tandem mass spectrometry. Over the 4 years, 1,233 oral fluid samples were collected. With respect to self-reported drug use, 63% of respondents reported medicinal and/or recreational drug use within the last week. When comparing 4 years of data from Miami (2014 to 2017), NPS trends showed the disappearance of alpha-PVP after 2014 followed by a significant increase in ethylone positivity in 2015 and rapid decrease in 2016. Dibutylone was identified for the first time in Miami 2016, and N-ethyl pentylone was identified for the first time in Miami 2017. Additionally, 3,4-methylenendioxymethamphetamine positivity steadily increased from 2014 to 2017. A comparison across study sites (Miami, Tampa and Atlanta) and specific trends with respect to novel simulant use are described within. Using this opportunistic approach of monitoring drug trends, we have found that peak positivity of novel stimulants usually is within a year of their first detection. Understanding the dynamics of NPS drug markets will allow laboratories to plan for resource allocation and scope updates within a timely fashion to assist with the detection and confirmation of these emerging substances in samples submitted for forensic analysis.

U-47700 and Its Analogs: Non-Fentanyl Synthetic Opioids Impacting the Recreational Drug Market.

The recreational use of opioid drugs is a global threat to public health and safety. In particular, an epidemic of opioid overdose fatalities is being driven by illicitly manufactured fentanyl, while novel synthetic opioids (NSOs) are appearing on recreational drug markets as standalone products, adulterants in heroin, or ingredients in counterfeit drug preparations. Trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) is a prime example of a non-fentanyl NSO that is associated with numerous intoxications and fatalities. Here, we review the medicinal chemistry, preclinical pharmacology, clandestine availability, methods for detection, and forensic toxicology of U-47700 and its analogs. An up-to-date summary of the human cases involving U-47700 intoxication and death are described. The evidence demonstrates that U-47700 is a potent µ-opioid receptor agonist, which poses a serious risk for overdosing and death. However, most analogs of U-47700 appear to be less potent and have been detected infrequently in forensic specimens. U-47700 represents a classic example of how chemical entities from the medicinal chemistry or patent literature can be diverted for use in recreational drug markets. Lessons learned from the experiences with U-47700 can inform scientists, clinicians, and policymakers who are involved with responding to the spread and impact of NSOs.

Analysis of 2,4-Dinitrophenol in Postmortem Blood and Urine by Gas Chromatography-Mass Spectrometry: Method Development and Validation and Report of Three Fatalities in the United States.

2,4-dinitrophenol (2,4-DNP) is a compound used in the early 1900s as a weight-loss drug but later prohibited due to its severe adverse effects, including death. It has however been attracting interest, due to its weight-loss properties, and appears to be re-emerging in forensic casework. As 2,4-DNP is available for use in industry and as a pesticide and easily accessible online, the dissemination of this drug can be fast. The compound exerts its effects through inhibition of ATP synthesis, and corresponding thermogenic energy loss which can be fatal. A method for qualitative and quantitative analysis of 2,4-DNP in blood and urine specimens using GC-MS with hydrogen as carrier gas is described. The method was validated and displayed acceptable performance parameters with linearity (R2 higher than 0.998), inter-assay imprecision (lower than 10.6%), intra-assay imprecision (lower than 10.7%), and extraction efficiency (92.1%). Stability of 2,4-DNP in blood and urine was studied, and the drug was stable up to 30 days refrigeration or frozen. Six cases in United States suspected to be related to 2,4-DNP were analyzed. Three cases were found to be positive for 2,4-DNP. Concentrations of 2,4-DNP were in the range of 61.6-220 mg/L in urine and <3-114 mg/L in blood. Based on our findings, we suggest that medical examiners and forensic toxicologists be aware of the reappearance of 2,4-DNP, including this compound as a target in death investigations related to weight-loss drugs.

Genomic insights from the first chromosome-scale assemblies of oat (Avena spp.) diploid species.

BACKGROUND: Cultivated hexaploid oat (Common oat; Avena sativa) has held a significant place within the global crop community for centuries; although its cultivation has decreased over the past century, its nutritional benefits have garnered increased interest for human consumption. We report the development of fully annotated, chromosome-scale assemblies for the extant progenitor species of the As- and Cp-subgenomes, Avena atlantica and Avena eriantha respectively. The diploid Avena species serve as important genetic resources for improving common oat's adaptive and food quality characteristics. RESULTS: The A. atlantica and A. eriantha genome assemblies span 3.69 and 3.78 Gb with an N50 of 513 and 535 Mb, respectively. Annotation of the genomes, using sequenced transcriptomes, identified ~ 50,000 gene models in each species-including 2965 resistance gene analogs across both species. Analysis of these assemblies classified much of each genome as repetitive sequence (~ 83%), including species-specific, centromeric-specific, and telomeric-specific repeats. LTR retrotransposons make up most of the classified elements. Genome-wide syntenic comparisons with other members of the Pooideae revealed orthologous relationships, while comparisons with genetic maps from common oat clarified subgenome origins for each of the 21 hexaploid linkage groups. The utility of the diploid genomes was demonstrated by identifying putative candidate genes for flowering time (HD3A) and crown rust resistance (Pc91). We also investigate the phylogenetic relationships among other A- and C-genome Avena species. CONCLUSIONS: The genomes we report here are the first chromosome-scale assemblies for the tribe Poeae, subtribe Aveninae. Our analyses provide important insight into the evolution and complexity of common hexaploid oat, including subgenome origin, homoeologous relationships, and major intra- and intergenomic rearrangements. They also provide the annotation framework needed to accelerate gene discovery and plant breeding.

4F-MDMB-BINACA: A New Synthetic Cannabinoid Widely Implicated in Forensic Casework.

This is the first report regarding the characterization of the new synthetic cannabinoid 4F-MDMB-BINACA. 4F-MDMB-BINACA was first analytically confirmed in seized drug material using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF), and nuclear magnetic resonance (NMR) spectroscopy. Subsequent to this characterization, 4F-MDMB-BINACA was detected in biological specimens collected as part of forensically relevant casework, including medicolegal death investigations and drug impaired driving investigations, from a variety of regions in the United States. Further analysis of biological specimens resulted in the identification of the metabolites 4F-MDMB-BINACA 3,3-dimethylbutanoic acid and 4-OH-MDMB-BINACA. 4F-MDMB-BINACA is appearing with increasing frequency as a contributory factor in deaths, creating morbidity and mortality risks for drug users. Laboratories must be aware of its presence and impact, incorporating 4F-MDMB-BINACA into workflows for detection and confirmation.

Chromatographic separation of the isobaric compounds cyclopropylfentanyl, crotonylfentanyl, methacrylfentanyl, and para-methylacrylfentanyl for specific confirmation by LC-MS/MS.

Cyclopropylfentanyl has been encountered by law enforcement and public health officials beginning in mid-2017 and has been associated with numerous overdoses and fatalities. The detection and identification of cyclopropylfentanyl has become more challenging with the subsequent emergence of multiple structural isomeric fentanyl species, some of which have been detected in seized drug casework. These include crotonylfentanyl, methacrylfentanyl, para-methylacrylfentanyl, and ortho-methylacrylfentanyl; all of which have the same exact mass and similar fragmentation patterns. Since these compounds may be scheduled differently and pharmacologically act differently, it is important to be able to differentiate them analytically. Our method was developed and validated for the analysis and differentiation of cyclopropylfentanyl from its isomers by liquid chromatography tandem mass spectrometry (LC-MS/MS), in order to confirm the identify of cyclopropylfentanyl in biological specimens from death investigation casework; 36 postmortem blood samples were submitted for analysis. Cyclopropylfentanyl, crotonylfentanyl, methacrylfentanyl, and para-methylacrylfentanyl were successfully resolved using a 13-minute run time and a simple gradient elution. Ortho-methacrylfentanyl was resolved only in a 20-minute chromatographic run. The assay met validation performance characteristics, with an analytical range of 1-100 ng/mL and limits of detection of 0.1 ng/mL for all analytes. Analysis of commonly encountered substances showed no interferences. All samples previously reported positive for cyclopropylfentanyl were confirmed positive for cyclopropylfentanyl in the absence of its isomers. To our knowledge to date, no positive toxicological specimens have been encountered for any cyclopropylfentanyl isomers.

Determination of cutting agents in seized cocaine samples using GC-MS, GC-TMS and LC-MS/MS.

Cocaine is usually sold as a white powder and can contain several adulterants and diluents, known as cutting agents. The cutting agents play an important role in the identification of trafficking routes, and they can also modify or intensify signs and symptoms of drug intoxication increasing the risk to the health's user. The purpose of this work was to quantify cocaine and cutting agents in 116 illicit samples from NMS Labs, Willow Grove, PA, U.S. Gas chromatography - mass spectrometry (GC-MS) and handle-portable gas chromatography toroidal ion trap mass spectrometry (GC-TMS) were used as screening methods A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of cocaine, levamisole, benzocaine, phenacetin, hydroxyzine, theophylline, diltiazem, acetaminophen and caffeine. Cocaine-d3 and caffeine-d3 were used as internal standards. The method was shown to be precise, accurate and linear over a range of 50-2000ng/mL for all analytes. Cocaine was the only detected compound in 16.37% (n=19) of the samples. Between the identified cutting agents, levamisole was the most abundant substance found (79.31% of the total samples, amounts ranging from 0.2 to 74.3%), followed by phenacetin (18.96%, 0.3-46.8%), caffeine (12.06%, 0.2-32.2%), hydroxyzine (9.48%, 0.7-13.8%) and benzocaine (5.17%, 0.4-58.3%). GC-TMS was considered suitable to be used as a tool in forensic analysis as a screening method for cocaine, benzocaine, phenacetin, hydroxyzine and caffeine with restrictions to be used for levamisole, while GC-MS presented good results in screening analysis for cocaine, levamisole, benzocaine, phenacetin, hydroxyzine and caffeine.

The Detection of Novel Stimulants in Oral Fluid from Users Reporting Ecstasy, Molly and MDMA Ingestion.

"Ecstasy" and "Molly" are common drug slang terms used among club and rave cultures to denote preparations believed to contain 3,4-methylenedioxymethamphetamine (MDMA). However, users of Ecstasy and Molly have increasingly tested positive for novel psychoactive substances (NPS), notably novel stimulants. To evaluate hypothesized non-specific and interchangeable use of the terms Ecstasy, Molly and MDMA, self-reported drug use was compared against toxicological findings in biological specimens. Oral fluid specimens were collected from participants attending large multi-day electronic dance music festivals in Miami, FL; Tampa, FL; and Atlanta, GA. Participants additionally completed a structured survey about recent recreational drug use. Collected specimens were screened for therapeutic drugs, common drugs of abuse and NPS using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF). Positive screen results were confirmed by validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods for MDMA, MDA, methylone, dimethylone, ethylone, butylone, dibutylone, eutylone, pentylone, N-ethyl pentylone (ephylone), alpha-PVP and 4-fluoroamphetamine (4-FA). During this 4-year study, 223 participants provided an oral fluid specimen and indicated recent use of Ecstasy, Molly and/or MDMA/MDA. Of these subjects, 203 (91.0%) indicated only one of these drug terms; while 20 (9.0%) participants indicated a combination of multiple terms. Of the 203 participants designating only one drug term, 123 (60.6%) reported Molly use, 55 (27.1%) reported MDMA use and 25 (12.3%) reported Ecstasy use. Seven participants reported the use of MDA, but these responses were paired with MDMA responses due to detection of MDA as a metabolite of MDMA. The results from this study indicate that there are inconsistencies between admission to drug use and toxicological findings in this population. Of the 223 participants who indicated use of Ecstasy, Molly and/or MDMA/MDA, MDMA without a novel stimulant was confirmed in 121 (54.3%) participants, while 66 (29.6%) tested positive for at least one novel stimulant.

Analysis of cis and trans 3-methylfentanyl by liquid chromatography-high resolution mass spectrometry and findings in forensic toxicology casework.

3-methylfentanyl (3-MF), N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide, has reappeared on the US illicit drug market since its disappearance after a series of overdose deaths in 1988. 3-MF presents an analytical challenge, due to presence of cis and trans stereoisomers, each with different potencies, and ultimately very low concentrations in the blood after use. A method was developed using liquid chromatography-time-of-flight-mass spectrometry for the analysis of (±)-cis-3-MF and (±)-trans-3-MF in blood specimens after solid phase extraction. The linear dynamic range of this method was 0.1-10 ng/mL. Blood samples from 25 postmortem cases and 2 human performance case involving 3-MF were submitted for quantitative analysis. The mean and median concentration for the (±)-cis-3-MF were 0.84 ng/mL (±0.81) and 0.67 ng/mL, respectively, range 0.14-3.43 ng/mL. The resulting (±)-trans-3-MF mean concentration was 0.46 ng/mL (±0.38) and the median concentration was 0.37 ng/mL with a range of 0.11-1.90 ng/mL. The resulting (±)-cis-3-MF and (±)-trans-3-MF concentrations were summed to give the total amount of 3-MF present in the case with the resulting average concentration at 1.28 ng/mL (±1.16), median at 1.01 ng/mL and range 0.18-5.18. As the estimated dose of this compound is approximately 0.1 mg-0.5 mg with the resulting concentrations in the sub-nanogram range, it is necessary for forensic toxicology laboratories to obtain instruments sensitive enough to detect these substances in driving under the influence of drugs and postmortem cases. Quantitation of 3-MF with separation of (±)-cis and (±)-trans-3-MF provides additional detail for more specific toxicological interpretation.