scholarly journals LC-QTOF-MS Identification of Major Urinary Cyclopropylfentanyl Metabolites Using Synthesized Standards

2019 ◽  
Vol 43 (8) ◽  
pp. 607-614 ◽  
Author(s):  
Svante Vikingsson ◽  
Tobias Rautio ◽  
Jakob Wallgren ◽  
Anna Åstrand ◽  
Shimpei Watanabe ◽  
...  
Keyword(s):  
United States ◽  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
The United States ◽  
Urine Samples ◽  
Post Mortem ◽  
Urinary Markers ◽  
Flight Mass Spectrometry ◽  
Fentanyl Analogs ◽  
Synthesis Routes

Abstract Cyclopropylfentanyl is a fentanyl analog implicated in 78 deaths in Europe and over 100 deaths in the United States, but toxicological information including metabolism data about this drug is scarce. The aim of this study was to provide the exact structure of abundant and unique metabolites of cyclopropylfentanyl along with synthesis routes. In this study, metabolites were identified in 13 post-mortem urine samples using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Samples were analyzed with and without enzymatic hydrolysis, and seven potential metabolites were synthesized in-house to provide the identity of major metabolites. Cyclopropylfentanyl was detected in all samples, and the most abundant metabolite was norcyclopropylfentanyl (M1) that was detected in 12 out of 13 samples. Reference materials were synthesized (synthesis routes provided) to identify the exact structure of the major metabolites 4-hydroxyphenethyl cyclopropylfentanyl (M8), 3,4-dihydroxyphenethyl cyclopropylfentanyl (M5) and 4-hydroxy-3-methoxyphenethyl cyclopropylfentanyl (M9). These metabolites are suitable urinary markers of cyclopropylfentanyl intake as they are unique and detected in a majority of hydrolyzed urine samples. Minor metabolites included two quinone metabolites (M6 and M7), not previously reported for fentanyl analogs. Interestingly, with the exception of norcyclopropylfentanyl (M1), the metabolites appeared to be between 40% and 90% conjugated in urine. In total, 11 metabolites of cyclopropylfentanyl were identified, including most metabolites previously reported after hepatocyte incubation.

Emerging Synthetic Cannabinoids: Development and Validation of a Novel Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry Assay for Real-Time Detection

2019 ◽  
Vol 44 (3) ◽  
pp. 207-217 ◽  
Author(s):  
Alex J Krotulski ◽  
Amanda L A Mohr ◽  
Barry K Logan
Keyword(s):  
United States ◽  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Real Time ◽  
Synthetic Cannabinoids ◽  
Time Of Flight ◽  
Forensic Toxicology ◽  
The United States ◽  
Synthetic Cannabinoid ◽  
Flight Mass Spectrometry

Abstract Synthetic cannabinoids pose significant threats to public health and safety, as their implications in overdose and adverse events continue to arise in United States and around the world. Synthetic cannabinoids have seen several generations of chemically diverse structural elements, impacting potency and effects. These factors create new analytical challenges for forensic laboratories. This report describes an efficient liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) assay for the identification of synthetic cannabinoid parent compounds and metabolites, including real-time identification of emergent compounds, using a SCIEX TripleTOF® 5600+ with non-targeted SWATH® acquisition. Method validation evaluated precision/accuracy, limits of detection, interferences, processed sample stability and carryover, for which 19 parent compounds and 19 metabolites were tested. To demonstrate feasibility, de-identified blood sample extracts were acquired from a large forensic toxicology laboratory and analyzed using the validated LC-QTOF-MS assay. In mid-2018, 200 blood extracts were analyzed, demonstrating a 19% positivity rate with > 94% agreement rate with original testing. In addition, three newly discovered synthetic cannabinoids were identified, including 5F-MDMB-PICA, 4-cyano CUMYL-BUTINACA and 5F-EDMB-PINACA. These synthetic cannabinoids were previously unreported in forensic toxicology casework in the United States. 5F-MDMB-PICA has become the most prevalent synthetic cannabinoid in United States, as of early 2019. These results demonstrate the effectiveness of this assay and workflow in the identification and characterization of synthetic cannabinoids, as well as the usefulness of sample-mining using non-targeted mass acquisition by LC-QTOF-MS for the discovery of NPS. High resolution mass spectrometry should be considered when developing new or novel assays for synthetic cannabinoids.

Verification of propofol sulfate as a further human propofol metabolite using LC-ESI-QQQ-MS and LC-ESI-QTOF-MS analysis

2017 ◽  
Vol 32 (1) ◽  
Author(s):  
Alexandra Maas ◽  
Christoph Maier ◽  
Beate Michel-Lauter ◽  
Sebastian Broecker ◽  
Burkhard Madea ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Electrospray Ionization ◽  
Phase Ii ◽  
Method Development ◽  
Urine Samples ◽  
Hydroxyl Group ◽  
Reference Standard ◽  
Detection Techniques ◽  
Flight Mass Spectrometry

AbstractBackground:Propofol (2,6-diisopropylphenol) is a water-insoluble, intravenous anesthetic that is widely used for the induction and maintenance of anesthesia as well as for endoscopic and pediatric sedation. After admission, propofol undergoes extensive hepatic and extrahepatic metabolism, including direct conjugation to propofol glucuronide and hydroxylation to 2,6-diisopropyl-1,4-quinol. The latter substance subsequently undergoes phase II metabolism, resulting in the formation of further metabolites (1quinolglucuronide, 4quinolglucuronide and 4quinol-sulfate). Further minor phase I propofol metabolites (2-(ω-propanol)-6-isopropylphenol and 2-(ω-propanol)-6-isopropyl-1,4-quinol)) are also described. Due to its chemical structure with the phenolic hydroxyl group, propofol is also an appropriate substrate for sulfation by sulfotransferases.Methods:The existence of propofol sulfate was investigated by liquid chromatography electrospray ionization triple quadrupole mass spectrometry (LCESIQQQ-MS) and liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LCESI-QTOF-MS). A propofol sulfate reference standard was used for identification and method development, yielding a precursor atResults:Propofol sulfate – a further phase II metabolite of propofol – was verified in urine samples by LC-ESI-QQQ-MS and LC-ESI-QTOF-MS. Analyses of urine samples from five volunteers collected before and after propofol-induced sedation verified the presence of propofol sulfate in urine following propofol administration, whereas ascertained concentrations of this metabolite were significantly lower compared with detected propofol glucuronide concentrations.Conclusions:The existence of propofol sulfate as a further phase II propofol metabolite in humans could be verified by two different detection techniques (LCESIQQQ-MS and LC-ESI-QTOFMS) on the basis of a propofol sulfate reference standard. Evaluation of the quantitative analyses of propofol sulfate imply that propofol sulfate represents a minor metabolite of propofol and is only slightly involved in human propofol clearance.

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 Quality Assessment of U.S. Marketplace Vancomycin for Injection Products Using High-Resolution Liquid Chromatography-Mass Spectrometry and Potency Assays

2012 ◽  
Vol 56 (6) ◽  
pp. 2824-2830 ◽  
Author(s):  
Michael E. Hadwiger ◽  
Cynthia D. Sommers ◽  
Daniel J. Mans ◽  
Vikram Patel ◽  
Michael T. Boyne
Keyword(s):  
United States ◽  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
The United States ◽  
United States Pharmacopeia ◽  
Chromatography Method ◽  
Vancomycin Hydrochloride ◽  
States Pharmacopeia

ABSTRACTIn response to a published concern about the potency and quality of generic vancomycin products, the United States Food and Drug Administration investigated a small sampling of the vancomycin products available in North America with regard to purity, content, and potency. To facilitate identification of impurities, a new liquid chromatography method was developed using high-resolution mass spectrometry in addition to diode array detection to characterize impurities in several commercial products. Furthermore, a microbiological assay was utilized to link the analytical profiles with anin vitropotency. All products tested met the quality specifications outlined in the United States Pharmacopeia (USP) (vancomycin hydrochloride for injection monograph) for impurities and potency (USP, Vancomycin hydrochloride for injection. United States Pharmacopeia and National Formulary, vol USP 34-NF 29, 2011).

Determination of amphenicol antibiotics and their glucuronide metabolites in urine samples using liquid chromatography with quadrupole time-of-flight mass spectrometry

2020 ◽  
Vol 1146 ◽  
pp. 122122
Author(s):  
Marta Pastor-Belda ◽  
Natalia Campillo ◽  
Natalia Arroyo-Manzanares ◽  
Manuel Hernández-Córdoba ◽  
Pilar Viñas
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Time Of Flight ◽  
Urine Samples ◽  
Flight Mass Spectrometry
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