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1.
JAMA ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230918

RESUMEN

This Viewpoint discusses the spread of medetomidine in the US illicit opioid market and the need for monitoring and a public health response.

3.
J Am Coll Emerg Physicians Open ; 5(4): e13235, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39161754

RESUMEN

Background: United States drug overdose deaths are being driven by the increasing prevalence of fentanyl, but whether patients are knowingly using fentanyl is unclear. We examined the analytical confirmation of fentanyl in emergency department (ED) patients with documented heroin overdose. Hypothesis: We hypothesized that the proportion of fentanyl and fentanyl analogs would be higher than that of confirmed heroin. Methods: This is a subgroup analysis from a prospective multicenter consecutive cohort of ED patients age 18+ with opioid overdose presenting to 10 US sites within the Toxicology Investigators Consortium from 2020 to 2021. Toxicology analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. De-identified toxicology results were paired with the clinical database. The primary outcome was the proportion of patients with fentanyl analytes detected in their serum. Results: Of 1006 patients screened, 406 were eligible, and of 168 patients who reported that they had taken heroin or had a documented heroin overdose, 88% (n = 147) were in fact found to have fentanyl and/or a fentanyl analog present on serum analysis (p < 0.0001). In contrast, only 46 of the 168 patients with reported or documented heroin overdose (27%) were found to have heroin biomarkers present. Conclusion: The prevalence of confirmed fentanyl in ED patients with suspected heroin overdose was extremely high, while the prevalence of heroin was very low. There was a high degree of mismatch between the opioids believed to be the overdose agent versus the actual opioids identified on serum toxicology. Clinicians in the United States should presume that fentanyl is involved in all illicit opioid overdoses and should counsel patients on harm reduction measures.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39018467

RESUMEN

ABSTRACT: Since January 2023, a series of fatalities has occurred in the Cook County Jail. Upon reviewing surveillance videos, in some cases, the inmates shared paper strips, and it was followed by the onset of labored breathing and loss of consciousness. Scene investigation revealed burnt paper strips near the body in 3 cases. No trauma was observed during autopsy. The expanded toxicology panels did not detect any illegal drugs in the postmortem blood samples. However, additional analysis specifically targeting synthetic cannabinoids revealed the presence of MDMB-4en-PINACA [methyl 3,3-dimethyl-2-{[1-(pent-4-en-1-yl)-1H-indazole-3-carbonyl]amino}butanoate], a synthetic cannabinoid associated with a wide range of adverse effects, including cardiovascular complications such as tachycardia and hypertension, respiratory depression, and acute kidney injury. There is limited research on the lethality of MDMB-4en-PINACA. This case series suggests that even isolated use can potentially lead to death. This study aims to raise public awareness regarding MDMB-4en-PINACA, highlighting its unpredictable effects and potential for severe adverse reactions, and to facilitate the development of effective prevention and harm reduction strategies. Implementing screening methods in correctional facilities is crucial to prevent the circulation of potentially fatal substances.

5.
Drug Alcohol Depend Rep ; 11: 100247, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974777

RESUMEN

Background: Xylazine is an ⍺2 adrenergic receptor agonist and a veterinary sedative that can cause severe health complications yet interventions to detect and treat human exposure remain underdeveloped. Community-based drug checking services (DCS) involve the testing of small amounts of drugs to increase community knowledge of unregulated supplies and decrease harms. This study characterized xylazine awareness, desire, use and exposure among people who use drugs (PWUD) in Rhode Island, US. Methods: We analyzed data from an ongoing PWUD cohort study. In 2023, 125 PWUD were enrolled and surveyed. Using point-of-care Fourier Transform infrared spectroscopy (FTIR-S), we tested a drug sample from each participant onsite and confirmed the results offsite at a laboratory. Results were conveyed in real-time, along with harm reduction education, referrals to resources and care. Results: Virtually all participants (99.2 %) wanted to avoid xylazine exposure. Half (51.2 %) knew what xylazine was, and a quarter (26.1 %) suspected previous exposure. Xylazine exposure was primarily surmised through sedating (45.2 %) and ulcerative (29.0 %) effects. Only 8.8 % of participants submitted a sample that they expected to contain xylazine. Xylazine was detected in 14.5 % of samples using FTIR-S and in 21.4 % of samples using a dual laboratory approach of gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Participants thought that these xylazine-positive samples were fentanyl (78.3 %), heroin (13.0 %), or Percocet® (8.7 %). Conclusion: Implementing point-of-care DCS at harm reduction organizations could be useful in rapidly increasing xylazine awareness and engaging at-risk individuals in prevention, harm reduction, treatment, and rapid care for xylazine-related wounds.

6.
Arch Toxicol ; 98(9): 2999-3018, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38877156

RESUMEN

2-Benzylbenzimidazole 'nitazene' opioids are presenting a growing threat to public health. Although various nitazenes were previously studied, systematic comparisons of the effects of different structural modifications to the 2-benzylbenzimidazole core structure on µ-opioid receptor (MOR) activity are limited. Here, we assessed in vitro structure-activity relationships of 9 previously uncharacterized nitazenes alongside known structural analogues. Specifically, we focused on MOR activation by 'ring' substituted analogues (i.e., N-pyrrolidino and N-piperidinyl modifications), 'desnitazene' analogues (lacking the 5-nitro group), and N-desethyl analogues. The results from two in vitro MOR activation assays (ß-arrestin 2 recruitment and inhibition of cAMP accumulation) showed that 'ring' modifications overall yield highly active drugs. With the exception of 4'-OH analogues (which are metabolites), N-pyrrolidino substitutions were generally more favorable for MOR activation than N-piperidine substitutions. Furthermore, removal of the 5-nitro group on the benzimidazole ring consistently caused a pronounced decrease in potency. The N-desethyl modifications showed important MOR activity, and generally resulted in a slightly lowered potency than comparator nitazenes. Intriguingly, N-desethyl isotonitazene was the exception and was consistently more potent than isotonitazene. Complementing the in vitro findings and demonstrating the high harm potential associated with many of these compounds, we describe 85 forensic cases from North America and the United Kingdom involving etodesnitazene, N-desethyl etonitazene, N-desethyl isotonitazene, N-pyrrolidino metonitazene, and N-pyrrolidino protonitazene. The low-to-sub ng/mL blood concentrations observed in most cases underscore the drugs' high potencies. Taken together, by bridging pharmacology and case data, this study may aid to increase awareness and guide legislative and public health efforts.


Asunto(s)
Analgésicos Opioides , Bencimidazoles , Relación Estructura-Actividad , Humanos , Bencimidazoles/química , Bencimidazoles/farmacología , Analgésicos Opioides/farmacología , Analgésicos Opioides/química , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Células HEK293 , Animales , Nitrocompuestos/química
7.
J Pharm Biomed Anal ; 247: 116254, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38810333

RESUMEN

Synthetic cannabinoids are a class of novel psychoactive substances that emerged in the drug market in the early 2010s. Since then, a wide range of different synthetic cannabinoids has been detected in drug materials and in biological specimens collected from intoxication cases. In general, synthetic cannabinoids are reported first in seized materials. In this study, the identification of the novel synthetic cannabinoid, ADB-5'Br-BINACA is reported. A plant material suspected to contain a synthetic cannabinoid was extracted and analyzed. Analyses were performed using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and one dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. An aliquot of the sample was extracted using methanol and deuterated chloroform, and analyzed via GC-MS and NMR, respectively. Further dilution of the methanolic extract was analyzed via LC-QTOF-MS. For ATR-FTIR analyses, a few drops of the extract in deuterated chloroform were analyzed. GC-MS, LC-QTOF-MS, and 1H NMRwere successfully used to elucidate and confirm the structure of ADB-5'Br-BINACA in the drug sample. ATR-FTIR and 13C NMR analyses of the extracts did not result in significant information for the confirmation of ADB-5'Br-BINACA in the plant material likely due to low amount of drug material and high background noise. The chemical characterization of ADB-5'Br-BINACA in an authentic sample is reported herein, and chromatographic, mass spectrometric and spectroscopic data are provided for use in future analysis of this drug in suspected samples.


Asunto(s)
Cannabinoides , Cromatografía de Gases y Espectrometría de Masas , Espectroscopía de Resonancia Magnética , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectroscopía de Resonancia Magnética/métodos , Cromatografía Liquida/métodos , Cannabinoides/análisis , Cannabinoides/química , Extractos Vegetales/química , Extractos Vegetales/análisis
8.
J Anal Toxicol ; 48(3): 141-149, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38437879

RESUMEN

Previous research has evaluated the extent to which cocaine and other drugs were detectable on currency in the USA. The literature was in agreement that the majority of bills exhibited some degree of contamination. With the increase of fentanyl in the illicit drug supply, this study was designed to evaluate the extent that fentanyl, cocaine, methamphetamine and other substances were present on circulating currency in 2022. A quantitative assay using liquid chromatography-triple quadrupole mass spectrometry was developed and validated to detect six analytes: fentanyl, 4-anilino-N-phenethylpiperidine, acetylfentanyl, benzylfentanyl, cocaine and methamphetamine. One-dollar bills were collected from 13 cities across the country. Sample preparation consisted of soaking the bills in methanol followed by liquid-liquid extraction. Chromatographic separation was achieved using a C18 analytical column and gradient elution with ammonium formate in water (5 mM, pH 3) and 0.1% formic acid in acetonitrile. The quantitative working range for this assay was 0.1 µg to 1.0 µg per bill (equivalent to 1 ng/mL to 100 ng/mL of extract). Fentanyl was detected on the majority (63%) of samples, with 61% of samples having ≥0.1 µg of fentanyl and 4% of samples having ≥1.0 µg. Cocaine and methamphetamine were detected on 100% and 98% of bills, respectively, typically in amounts >1.0 µg. The remaining fentanyl-related substances were detected in 15% of samples in amounts no >0.69 µg per bill and exclusively in the presence of fentanyl. Unsurprisingly, areas of the country with higher incidence of fentanyl use yielded higher frequency of contaminated bills and higher concentrations. Human exposure to drugs on currency is unlikely to have any significant impacts toxicologically or pharmacologically; however, our research findings suggest that paper currency could serve as a useful substrate for surveillance of drug trends regionally, nationally and/or internationally.


Asunto(s)
Cocaína , Drogas Ilícitas , Metanfetamina , Estados Unidos , Humanos , Fentanilo/análisis , Cocaína/análisis , Drogas Ilícitas/análisis , Contaminación de Medicamentos , Cromatografía Líquida de Alta Presión/métodos
9.
J Hazard Mater ; 469: 133955, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38457976

RESUMEN

The complexity around the dynamic markets for new psychoactive substances (NPS) forces researchers to develop and apply innovative analytical strategies to detect and identify them in influent urban wastewater. In this work a comprehensive suspect screening workflow following liquid chromatography - high resolution mass spectrometry analysis was established utilising the open-source InSpectra data processing platform and the HighResNPS library. In total, 278 urban influent wastewater samples from 47 sites in 16 countries were collected to investigate the presence of NPS and other drugs of abuse. A total of 50 compounds were detected in samples from at least one site. Most compounds found were prescription drugs such as gabapentin (detection frequency 79%), codeine (40%) and pregabalin (15%). However, cocaine was the most found illicit drug (83%), in all countries where samples were collected apart from the Republic of Korea and China. Eight NPS were also identified with this protocol: 3-methylmethcathinone 11%), eutylone (6%), etizolam (2%), 3-chloromethcathinone (4%), mitragynine (6%), phenibut (2%), 25I-NBOH (2%) and trimethoxyamphetamine (2%). The latter three have not previously been reported in municipal wastewater samples. The workflow employed allowed the prioritisation of features to be further investigated, reducing processing time and gaining in confidence in their identification.


Asunto(s)
Drogas Ilícitas , Contaminantes Químicos del Agua , Aguas Residuales , Flujo de Trabajo , Psicotrópicos , China , Contaminantes Químicos del Agua/análisis
11.
Sci Total Environ ; 920: 170781, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38360322

RESUMEN

Synthetic opioids, particularly the nitazene analogues class, have become a public health concern due to their high potency. Wastewater-based epidemiology can detect community use of these compounds. The objective of this work was to detect nitazene analogues in wastewater from samples collected from eight sites in the United States. Influent wastewater samples were collected from eight sites in seven states (Arizona, Oregon, New Mexico, Illinois, New Jersey, Washington and Georgia) in the United States. Samples were collected from each site on three days between 27 December 2022 and 4 January 2023, acidified on collection, stored frozen and shipped to Arizona State University (Tempe, AZ) for sample processing. Samples were then shipped to The University of Queensland (Brisbane, Australia) for sample analysis. Protonitazene was found in samples collected from two sites in Washington and Illinois. The concentration was estimated up to 0.5 ng/L, with estimated excreted mass loads up to 0.3 mg/day/1000 people. This work has shown that it is possible to detect nitazene analogues in wastewater using a combination of sample pre-concentration and sensitive instrumentation, thereby further expanding the utility of wastewater-based epidemiology.


Asunto(s)
Drogas Ilícitas , Contaminantes Químicos del Agua , Humanos , Drogas Ilícitas/análisis , Aguas Residuales , Monitoreo Epidemiológico Basado en Aguas Residuales , Australia , Arizona , Contaminantes Químicos del Agua/análisis
12.
Drug Test Anal ; 16(4): 380-391, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37491777

RESUMEN

The rapidly evolving synthetic cannabinoid receptor agonist (SCRA) market poses significant challenges for forensic scientists. Since the enactment of a generic ban in China, a variety of new compounds have emerged capable of evading the legislation by carrying new structural features. One recent example of a SCRA with new linker and head moieties is CH-PIATA (CH-PIACA, CHX-PIATA, CHX-PIACA). CH-PIATA bears an additional methylene spacer in the linker moiety between the indole core and the traditional carbonyl component of the linker. This study describes detections in 2022 of this new SCRA in the United States, Belgium, and Scottish prisons. CH-PIATA was detected once in a seized powder by Belgian customs and 12 times in Scottish prisons in infused papers or resin. The metabolites of CH-PIATA were investigated via in vitro human liver microsome (HLM) incubations and eight metabolites were identified, dominated by oxidative biotransformations. A blood sample from the United States was confirmed to contain a mixture of SCRAs including CH-PIATA via presence of the parent and at least five of the metabolites identified from HLM incubations. Furthermore, this paper evaluates the intrinsic in vitro cannabinoid 1 and 2 (CB1 and CB2) receptor activation potential of CH-PIATA reference material and the powder seized by Belgian customs by means of ß-arrestin 2 recruitment assays. Both the reference and the seized powder showed a weak activity at both CB receptors with signs of antagonism found. Based on these results, the expected harm potential of this newly emerging substance remains limited.


Asunto(s)
Cannabinoides , Ácidos Indolacéticos , Humanos , Polvos , Agonistas de Receptores de Cannabinoides/química , Receptores de Cannabinoides , Receptor Cannabinoide CB1 , Receptor Cannabinoide CB2
13.
Drug Test Anal ; 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037247

RESUMEN

Synthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances (NPS) and new structural scaffolds have emerged on the recreational drug market since the enactment of Chinese SCRA analog controls in 2021. This study reports the first SCRAs to be detected with a bromide at the 5 position (5'Br) on the phenyl ring of the indazole core and without a tail moiety. ADB-5'Br-INACA (ADMB-5'Br-INACA) and MDMB-5'Br-INACA were detected in seized samples from Scottish prisons, Belgian customs, and US forensic casework. The brominated analog with a tail moiety, ADB-5'Br-BUTINACA (ADMB-5'Br-BUTINACA), was also detected in Scottish prisons and US forensic casework. The metabolites of these compounds and the predicted compound MDMB-5'Br-BUTINACA were identified through incubation with primary human hepatocytes to aid in their toxicological identification. The bromide on the indazole remains intact on metabolites, allowing these compounds to be easily distinguished in toxicological samples from their non-brominated analogs. Glucuronidation was more common for tail-less analogs than their butyl tail-containing counterparts. Forensic toxicologists are advised to update their analytical methods with the characteristic ions for these compounds, as well as their anticipated urinary markers: amide hydrolysis and monoOH at tert-butyl metabolites (after ß-glucuronidase treatment) for ADB-5'Br-INACA; monoOH at tert-butyl and amide hydrolysis metabolites for ADB-5'Br-BUTINACA; and ester hydrolysis metabolites with additional metabolites for MDMB-5'Br-INACA and MDMB-5'Br-BUTINACA. Toxicologists should remain vigilant to the emergence of new SCRAs with halogenation of the indazole core and tail-less analogs, which have already started to emerge.

14.
JAMA Netw Open ; 6(8): e2331264, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37642962

RESUMEN

Importance: Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series. Objective: To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD. Design, Setting, and Participants: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis. Exposures: Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene. Main Outcomes and Measures: The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only. Results: During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation. Conclusions and Relevance: In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.


Asunto(s)
Sobredosis de Droga , Sobredosis de Opiáceos , Adulto , Femenino , Masculino , Humanos , Adulto Joven , Persona de Mediana Edad , Analgésicos Opioides , Estudios de Cohortes , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Droga/epidemiología , Fentanilo , Progresión de la Enfermedad , Servicio de Urgencia en Hospital
15.
J Anal Toxicol ; 47(8): 753-761, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37329303

RESUMEN

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).


Asunto(s)
Estimulantes del Sistema Nervioso Central , Cathinona Sintética , Toxicología Forense/métodos , Anfetamina
16.
Anal Bioanal Chem ; 415(21): 5165-5180, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37173408

RESUMEN

The emergence of structurally diverse new synthetic opioids (NSOs) has caused the opioid crisis to spiral to new depths. Little information is available about the pharmacology of most novel opioids when they first emerge. Here, using a ß-arrestin 2 recruitment assay, we investigated the in vitro µ-opioid receptor (MOR) activation potential of dipyanone, desmethylmoramide, and acetoxymethylketobemidone (O-AMKD) - recent NSOs that are structurally related to the prescription opioids methadone and ketobemidone. Our findings indicate that dipyanone (EC50=39.9 nM; Emax=155% vs. hydromorphone) is about equally active as methadone (EC50=50.3 nM; Emax=152%), whereas desmethylmoramide (EC50=1335 nM; Emax=126%) is considerably less active. A close structural analogue of ketobemidone (EC50=134 nM; Emax=156%) and methylketobemidone (EC50=335 nM; Emax=117%), O-AMKD showed a lower potency (EC50=1262 nM) and efficacy (Emax=109%). Evaluation of the opioid substitution product buprenorphine and its metabolite norbuprenorphine confirmed the increased in vitro efficacy of the latter. In addition to in vitro characterization, this report details the first identification and full chemical analysis of dipyanone in a seized powder, as well as a postmortem toxicology case from the USA involving the drug. Dipyanone was quantified in blood (370 ng/mL), in which it was detected alongside other NSOs (e.g., 2-methyl AP-237) and novel benzodiazepines (e.g., flualprazolam). While dipyanone is currently not commonly encountered in forensic samples worldwide, its emergence is worrisome and representative of the dynamic NSO market. Graphical Abstract.


Asunto(s)
Analgésicos Opioides , Medicamentos bajo Prescripción , Humanos , Analgésicos Opioides/farmacología , Analgésicos Opioides/química , Metadona
17.
J Forensic Sci ; 68(5): 1643-1661, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37221651

RESUMEN

Fentanyl, fentanyl analogs, and other novel synthetic opioids (NSO), including nitazene analogs, prevail in forensic toxicology casework. Analytical methods for identifying these drugs in biological specimens need to be robust, sensitive, and specific. Isomers, new analogs, and slight differences in structural modifications necessitate the use of high-resolution mass spectrometry (HRMS), especially as a non-targeted screening method designed to detect newly emerging drugs. Traditional forensic toxicology workflows, such as immunoassay and gas chromatography mass spectrometry (GC-MS), are generally not sensitive enough for detection of NSOs due to observed low (sub-µg/L) concentrations. For this review, the authors tabulated, reviewed, and summarized analytical methods from 2010-2022 for screening and quantification of fentanyl analogs and other NSOs in biological specimens using a variety of different instruments and sample preparation approaches. Limits of detection or quantification for 105 methods were included and compared to published standards and guidelines for suggested scope and sensitivity in forensic toxicology casework. Methods were summarized by instrument for screening and quantitative methods for fentanyl analogs and for nitazenes and other NSO. Toxicological testing for fentanyl analogs and NSOs is increasingly and most commonly being conducted using a variety of liquid chromatography mass spectrometry (LC-MS)-based techniques. Most of the recent analytical methods reviewed exhibited limits of detection well below 1 µg/L to detect low concentrations of increasingly potent drugs. In addition, it was observed that most newly developed methods are now using smaller sample volumes which is achievable due to the sensitivity increase gained by new technology and new instrumentation.


Asunto(s)
Analgésicos Opioides , Fentanilo , Analgésicos Opioides/análisis , Espectrometría de Masas en Tándem , Cromatografía Liquida , Cromatografía de Gases y Espectrometría de Masas , Detección de Abuso de Sustancias/métodos
18.
Clin Toxicol (Phila) ; 61(3): 173-180, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-37014353

RESUMEN

INTRODUCTION: Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures. METHODS: This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary). RESULTS: Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94). CONCLUSIONS: In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.


Asunto(s)
Sobredosis de Droga , Sobredosis de Opiáceos , Adulto , Humanos , Estados Unidos/epidemiología , Analgésicos Opioides , Xilazina , Estudios Prospectivos , Coma , Fentanilo , Sobredosis de Droga/diagnóstico , Sobredosis de Droga/epidemiología , Sobredosis de Droga/terapia , Servicio de Urgencia en Hospital
19.
Drug Test Anal ; 15(10): 1067-1076, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35347865

RESUMEN

Cannabinoid-based products submitted by consumers experiencing adverse effects were analyzed to identify and quantitate ingredients. Product testing identified several synthetic cannabinoids and products with inaccurate or incomplete labeling.


Asunto(s)
Cannabinoides , Vapeo , Dronabinol
20.
J Forensic Sci ; 68(1): 212-221, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36372911

RESUMEN

Novel synthetic opioid (NSO) continue to emerge in the United States in the midst of an opioid crisis. The NSO 2F-viminol was identified in casework at the Center for Forensic Science Research and Education through its NPS Discovery program in 2019. Little information and published literature were available for this new opioid at the time. To address this, human liver microsomes (HLMs) were used to perform in vitro metabolism studies with a drug standard. The goal was to predict in vivo metabolism. Experimental samples were prepared using HLMs, NADPH, phosphate buffer (pH 7.4), and a 2F-viminol standard. Standard samples were prepared containing only drug, control samples were prepared with drug and HLMs but no NADPH cofactor, and metabolism reaction mixtures contained drug, HLMs and NADPH. The subsequent mixtures were incubated with light shaking to allow metabolism to occur. After cleanup, metabolite mixtures were analyzed via a SCIEX TripleTOF 5600+ liquid chromatograph quadrupole-time-of-flight mass spectrometer (LC-QTOF-MS). The generated metabolic structures were elucidated using SCIEX MetabolitePilot software (version 2.0). In addition to remaining parent drug, seven metabolites of 2F-viminol were discovered, including N-dealkylated and hydroxylated species. The proposed primary metabolites of 2F-viminol were N-dealkylation (sec-butyl) + hydroxylation and N-dealkylation (sec-butyl); however, they should be confirmed in authentic samples, and forensic laboratories should consider adding 2F-viminol and its metabolites to screening protocols to help in extending the window of detection for the parent drug in toxicological samples. As NSOs continue to appear, forensic laboratories must continue metabolism experiments to generate information about pharmacokinetics.


Asunto(s)
Analgésicos Opioides , Microsomas Hepáticos , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Microsomas Hepáticos/metabolismo , Metaboloma
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