A Case Series of Etizolam in Opioid-Related Deaths

2020 ◽  
Author(s):  
Jirair Gevorkyan ◽  
Juliet Kinyua ◽  
Sue Pearring ◽  
Luke N Rodda
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Drug Toxicity ◽  
Case Series ◽  
Gastric Fluid ◽  
Multiple Drug ◽  
Flight Mass Spectrometry ◽  
Nonmedical Use ◽  
Liquid Chromatography Tandem Mass ◽  
Death Investigation

Abstract Etizolam is a novel psychoactive substance and novel benzodiazepine of the thienotriazolodiazepine class, which has recently seen an increasing trend in use worldwide. We report a case series of 10 decedents with etizolam and opioids in their systems. Death investigation, expanded toxicology and medical investigation information were included for contextualization of etizolam in death. Etizolam was detected and confirmed within peripheral and cardiac blood, urine, vitreous humor and, in one case, gastric fluid, by liquid chromatography–tandem mass spectrometry and liquid chromatography–quadrupole time of flight mass spectrometry methodologies. Death investigation indicated nonmedical use of most drugs. Medical investigation commonly noted pulmonary edema, cardiomegaly and cerebral swelling. The majority of the decedents appeared to be unaware of the presence of etizolam and succumbed to the mixed drug toxicity of their routine depressant and narcotic analgesic drug of abuse in combination with etizolam. Etizolam use continues to be observed and poses as a potentially lethal contribution to multiple drug toxicity, especially in the age of the opioid crisis. Assessment of analytes like etizolam requires up-to-date methodologies and vigilance in testing to better characterize the toxicology and interpret the contribution to death.

scholarly journals Case Series of Novel Illicit Opioid-Related Deaths

2017 ◽  
Vol 7 (3) ◽  
pp. 477-486 ◽  
Author(s):  
Donna Papsun ◽  
Amy Hawes ◽  
Amanda L.A. Mohr ◽  
Melissa Friscia ◽  
Barry K. Logan
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Whole Blood ◽  
High Performance ◽  
Case Series ◽  
Forensic Toxicology ◽  
Smoke Inhalation ◽  
Manner Of Death ◽  
Flight Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Novel illicit opioids, such as furanyl fentanyl and U-47700, are being encountered with increasing frequency in street heroin samples and have been confirmed in a series of overdose deaths in Tennessee. In this paper, we report the pathology and toxicology from 11 deaths involving furanyl fentanyl and U-47700. Routine toxicology was performed on postmortem femoral or antemortem hospital blood samples with targeted broad spectrum drug screening using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS). Confirmation and quantitation of the opioid agonists U-47700 and furanyl fentanyl was performed by ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using a novel method. Two cases were identified as containing U-47700 in whole blood (189 and 547 ng/mL), and nine cases contained furanyl fentanyl in whole blood, with concentrations ranging from 2.0 – 42.9 ng/mL. In all 11 cases, the manner of death was deemed accident, with drug intoxication being the primary cause of death; one case was complicated by smoke inhalation. All of the decedents were males ranging from 18-62 years, with the median age being 36 years old. The successful identification and confirmation of these novel illicit opioids in this case series relied on the comprehensive investigation and collaboration of scene investigation, forensic pathology, and forensic toxicology.

Concentrations of para-Fluorofuranylfentanyl (FFF) in Paired Central and Peripheral Blood Collected During Postmortem Death Investigations

2021 ◽  
Author(s):  
Judith Rodriguez Salas ◽  
Alex J Krotulski ◽  
Reta Newman ◽  
Jon R Thogmartin ◽  
Amanda L A Mohr ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Peripheral Blood ◽  
The United States ◽  
Blood Concentrations ◽  
Pinellas County ◽  
Flight Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Death Investigation ◽  
Medicolegal Death Investigation

Abstract The opioid epidemic in the United States (U.S.) has been associated with an increasing mortality rate in large part due to the emergence and proliferation of synthetic opioids over the last fifteen years. Fentanyl and its analogues have played a large part in these statistics due to their potency and toxicity. Fluorofuranylfentanyl (FFF) is a fentanyl analogue that emerged in the U.S. in 2018 and was associated with numerous adverse events and deaths. During this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) workflow was developed to accurately identify the isomer of FFF present (ortho- vs. meta- vs. para-) in medicolegal death investigation cases from Pinellas County, Florida. FFF was quantified in central and peripheral blood samples collected at autopsy. In addition, the metabolism of FFF was studied using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). para-FFF was quantitatively confirmed in 29 postmortem cases; no other isomer of FFF was detected. Central blood concentrations ranged between 0.66 and 73 ng/mL (mean = 11±14 ng/mL, median = 10 ng/mL) and peripheral blood concentrations ranged between 0.53 and 23 ng/mL (mean = 5.7±6.4 ng/mL, median = 2.7 ng/mL). Comparison of central to peripheral blood concentrations were evaluated to determine the possibility of postmortem redistribution (PMR). The metabolism of ortho-FFF was studied and found to undergo metabolic processes similar to fentanyl, producing ortho-fluorofuranyl-norfentanyl, fluoro-4-ANPP, and hydroxylated species. The results of this study demonstrate the toxicity of FFF and its implication in medicolegal death investigations. Laboratories must remain aware of new or re-emerging fentanyl analogues, as they pose significant risks to public health and public safety.

scholarly journals Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography–tandem mass spectrometry

2022 ◽  
Author(s):  
Koji Yamaguchi ◽  
Hajime Miyaguchi ◽  
Youkichi Ohno ◽  
Yoshimasa Kanawaku
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Pyridine Ring ◽  
Multiple Reaction Monitoring ◽  
Fragmentation Pattern ◽  
The Novel ◽  
Flight Mass Spectrometry ◽  
Urine Extract ◽  
Liquid Chromatography Tandem Mass ◽  
Characteristic Fragmentation

Abstract Purpose Zolpidem (ZOL) is a hypnotic sometimes used in drug-facilitated crimes. Understanding ZOL metabolism is important for proving ZOL intake. In this study, we synthesized standards of hydroxyzolpidems with a hydroxy group attached to the pyridine ring and analyzed them to prove their presence in postmortem urine. We also searched for novel ZOL metabolites in the urine sample using liquid chromatography–triple quadrupole mass spectrometry (LC-QqQMS) and liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QqTOFMS). Methods 7- and 8-Hydroxyzolpidem (7OHZ and 8OHZ, respectively) were synthesized and analyzed using LC-QqQMS. Retention times were compared between the synthetic standards and extracts of postmortem urine. To search for novel ZOL metabolites, first, the urine extract was analyzed with data-dependent acquisition, and the peaks showing the characteristic fragmentation pattern of ZOL were selected. Second, product ion spectra of these peaks at various collision energies were acquired and fragments that could be used for multiple reaction monitoring (MRM) were chosen. Finally, MRM parameters were optimized using the urine extract. These peaks were also analyzed using LC-QqTOFMS. Results The presence of 7OHZ and 8OHZ in urine was confirmed. The highest peak among hydroxyzolpidems was assigned to 7OHZ. The novel metabolites found were zolpidem dihydrodiol and its glucuronides, cysteine adducts of ZOL and dihydro(hydroxy)zolpidem, and glucuronides of hydroxyzolpidems. Conclusions The presence of novel metabolites revealed new metabolic pathways, which involve formation of an epoxide on the pyridine ring as an intermediate.

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

2020 ◽  
Author(s):  
Melissa F Fogarty ◽  
Amanda L A Mohr ◽  
Donna M Papsun ◽  
Barry K Logan
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Whole Blood ◽  
Solid Phase ◽  
Pharmaceutical Research ◽  
Case Series ◽  
Opioid Agonist ◽  
Structural Class ◽  
Human Whole Blood ◽  
Flight Mass Spectrometry

Abstract 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.

scholarly journals Occurrence of Free and Conjugated Mycotoxins in Aromatic and Medicinal Plants and Dietary Exposure Assessment in the Moroccan Population

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 125
Author(s):  
Aicha El Jai ◽  
Abdellah Zinedine ◽  
Ana Juan-García ◽  
Jordi Mañes ◽  
Samira Etahiri ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Medicinal Plants ◽  
Exposure Assessment ◽  
Agricultural Practices ◽  
Dietary Exposure ◽  
Flight Mass Spectrometry ◽  
Aromatic And Medicinal Plants ◽  
Liquid Chromatography Tandem Mass ◽  
Conjugated Mycotoxins

Aromatic and medicinal plants (AMPs), as herbal material, are subjected to contamination by various mycotoxin-producing fungi, either free and conjugated. Such a problem is associated with poor storage practices, and lack of adopting good agricultural practices and good harvesting practices. Nevertheless, AMPs are poorly investigated. The purpose of this study was to investigate the co-occurrence of 15 mycotoxins (four aflatoxins (AFB1, AFB2, AFG1, and AFG2), ochratoxin A (OTA), beauvericin (BEA), four enniatins (ENA, ENA1, ENB, and ENB1), zearalenone (ZEN), alternariol (AOH), tentoxin (TENT), T-2, and HT-2 toxins) in 40 samples of AMPs frequently consumed in Morocco by using liquid chromatography tandem mass spectrometry. Evaluation of conjugated mycotoxins and their identification using liquid chromatography coupled to time-of-flight mass spectrometry with ion mass exact was also carried out. Results showed that 90% of the analyzed samples presented at least one mycotoxin, and 52% presented co-occurrence of them. Mycotoxins detected were: AOH (85%), ZEN (27.5%), β-ZEL (22%), AFG1 (17.5%), TENT (17.5%), ENB (10%), AFG2 (7.5%), α-ZEL (5%), ENA1 (2.5%), and HT-2 (2.5%), while the conjugated mycotoxins were ZEN-14-Glc (11%) and ZEN-14-Sulf (9%). The highest observed level was for AOH, with 309 ng/g. Ten samples exceeded the recommended levels set by the European Pharmacopoeia for AF mycotoxins in plant material (4 ng/g), and three samples exceeded the maximum limits for AFs (10 ng/g) in species established by the European Commission. Although the co-occurrence of several mycotoxins in AMP samples was observed, the dietary exposure assessment showed that the intake of mycotoxins through the consumption of AMP beverages does not represent a risk for the population.

scholarly journals The Importance of Melatonin Detection in Pediatric Deaths

2019 ◽  
Vol 9 (1-2) ◽  
pp. 24-32 ◽  
Author(s):  
Laura M. Labay ◽  
James C. Kraner ◽  
Allen R. Mock ◽  
Thomas J. Sozio
Keyword(s):  
Mass Spectrometry ◽  
Gastric Fluid ◽  
Tandem Mass ◽  
Melatonin Concentration ◽  
Blood Samples ◽  
Exogenous Melatonin ◽  
News Reports ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Death Investigation

Melatonin is an endogenous hormone that regulates sleep patterns. It is available in varying formulations and dosages and is marketed as a natural substance that can alleviate insomnia. Recent news reports indicate that melatonin has been administered without appropriate authorization in daycare settings. Even though lethal outcomes have not been solely attributed to exogenous melatonin overdose, it has been relevant to select police and postmortem investigations. A quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the analysis of biological specimens. Results of 22 positive blood samples were evaluated based upon gender, age, and melatonin concentration from cases submitted by clinical, police, and death investigation agencies. Two cases are described. In Case 1, a 9-month-old was found unresponsive after cosleeping with a sibling. Allegations included exposure to an unspecified pesticide and dextromethorphan, and consumption of half a cigarette. There was admitted use of melatonin. Melatonin was quantified in blood and gastric fluid at concentrations of 13 ng/mL and 1200 ng/mL, respectively. In Case 2, a 13-month-old was found nonresponsive in a shared room. Melatonin was found within some of the sippy cups. The infant was extremely warm to the touch. Resuscitative efforts were unsuccessful and death was pronounce3d. Analysis showed a result of 210 ng/mL in blood. The presented quantitative LC-MS/MS method can successfully be applied to evaluate exposure to exogenous melatonin. Toxicology testing can assist in the investigation of these case types by substantiating the purposeful administration of melatonin.

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