scholarly journals Analysis of Synthetic Cannabinoids Using High-Resolution Mass Spectrometry and Mass Defect Filtering: Implications for Nontargeted Screening of Designer Drugs

2012 ◽  
Vol 84 (13) ◽  
pp. 5574-5581 ◽  
Author(s):  
Megan Grabenauer ◽  
Wojciech L. Krol ◽  
Jenny L. Wiley ◽  
Brian F. Thomas
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Synthetic Cannabinoids ◽  
Designer Drugs ◽  
Mass Defect ◽  
High Resolution Mass ◽  
Resolution Mass

scholarly journals Distinguishing Intake of New Synthetic Cannabinoids ADB-PINACA and 5F-ADB-PINACA with Human Hepatocyte Metabolites and High-Resolution Mass Spectrometry

2017 ◽  
Vol 63 (5) ◽  
pp. 1008-1021 ◽  
Author(s):  
Jeremy Carlier ◽  
Xingxing Diao ◽  
Karl B Scheidweiler ◽  
Marilyn A Huestis
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Legal Status ◽  
High Resolution Mass Spectrometry ◽  
Synthetic Cannabinoids ◽  
Analysis Data ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis ◽  
High Resolution Mass ◽  
Resolution Mass

Abstract BACKGROUND ADB-PINACA and its 5-fluoropentyl analog 5F-ADB-PINACA are among the most potent synthetic cannabinoids tested to date, with several severe intoxication cases. ADB-PINACA and 5F-ADB-PINACA have a different legal status, depending on the country. Synthetic cannabinoid metabolites predominate in urine, making detection of specific metabolites the most reliable way for proving intake in clinical and forensic specimens. However, there are currently no data on ADB-PINACA and 5F-PINACA metabolism. The substitution of a single fluorine atom distinguishes the 2 molecules, which may share common major metabolites. For some legal applications, distinguishing between ADB-PINACA and 5F-PINACA intake is critical. For this reason, we determined the human metabolic fate of the 2 analogs. METHODS ADB-PINACA and 5F-PINACA were incubated for 3 h with pooled cryopreserved human hepatocytes, followed by liquid chromatography—high-resolution mass spectrometry analysis. Data were processed with Compound Discoverer. RESULTS We identified 19 and 12 major ADB-PINACA and 5F-ADB-PINACA metabolites, respectively. Major metabolic reactions included pentyl hydroxylation, hydroxylation followed by oxidation (ketone formation), and glucuronidation of ADB-PINACA, and oxidative defluorination followed by carboxylation of 5F-ADB-PINACA. CONCLUSIONS We recommend ADB-PINACA ketopentyl and hydroxypentyl, and ADB-PINACA 5-hydroxypentyl and pentanoic acid, as optimal markers for ADB-PINACA and 5F-ADB-PINACA intake, respectively. Since the 2 compounds present positional isomers as the primary metabolites, monitoring unique product ions and optimized chromatographic conditions are required for a clear distinction between ADB-PINACA and 5F-ADB-PINACA intake.

scholarly journals Challenges of High-Resolution Mass Spectrometry For Detecting Designer Drugs

2020 ◽  
Vol 66 (7) ◽  
pp. 868-874 ◽  
Author(s):  
Frederick G Strathmann; ◽  
Kara L Lynch ◽  
Alex Krotulski ◽  
Pierre Negri ◽  
Julie Cichelli ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Designer Drugs ◽  
High Resolution Mass ◽  
Resolution Mass

scholarly journals High-Resolution Mass Spectrometry for Characterizing the Metabolism of Synthetic Cannabinoid THJ-018 and Its 5-Fluoro Analog THJ-2201 after Incubation in Human Hepatocytes

2016 ◽  
Vol 62 (1) ◽  
pp. 157-169 ◽  
Author(s):  
Xingxing Diao ◽  
Ariane Wohlfarth ◽  
Shaokun Pang ◽  
Karl B Scheidweiler ◽  
Marilyn A Huestis
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Adverse Events ◽  
High Resolution Mass Spectrometry ◽  
Synthetic Cannabinoids ◽  
Human Hepatocytes ◽  
Synthetic Cannabinoid ◽  
High Resolution Mass ◽  
Data Acquisition And Processing ◽  
Resolution Mass

Abstract BACKGROUND Despite increasing prevalence of novel psychoactive substances, no human metabolism data are currently available, complicating laboratory documentation of intake in urine samples and assessment of the drugs' pharmacodynamic, pharmacokinetic, and toxicological properties. In 2014, THJ-018 and THJ-2201, synthetic cannabinoid indazole analogs of JWH-018 and AM-2201, were identified, with the National Forensic Laboratory Information System containing 220 THJ-2201 reports. Because of numerous adverse events, the Drug Enforcement Administration listed THJ-2201 as Schedule I in January 2015. METHODS We used high-resolution mass spectrometry (HR-MS) (TripleTOF 5600+) to identify optimal metabolite markers after incubating 10 μmol/L THJ-018 and THJ-2201 in human hepatocytes for 3 h. Data were acquired via full scan and information-dependent acquisition triggered product ion scans with mass defect filter. In silico metabolite predictions were performed with MetaSite and compared with metabolites identified in human hepatocytes. RESULTS Thirteen THJ-018 metabolites were detected, with the major metabolic pathways being hydroxylation on the N-pentyl chain and further oxidation or glucuronidation. For THJ-2201, 27 metabolites were observed, predominantly oxidative defluorination plus subsequent carboxylation or glucuronidation, and glucuronidation of hydroxylated metabolites. Dihydrodiol formation on the naphthalene moiety was observed for both compounds. MetaSite prediction matched well with THJ-018 hepatocyte metabolites but underestimated THJ-2201 oxidative defluorination. CONCLUSIONS With HR-MS for data acquisition and processing, we characterized THJ-018 and THJ-2201 metabolism in human hepatocytes and suggest appropriate markers for laboratories to identify THJ-018 and THJ-2201 intake and link observed adverse events to these new synthetic cannabinoids.

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