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Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.
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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
Clinical Chemistry, 2015Co-Authors: Xingxing Diao, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Marilyn A HuestisAbstract: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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First Characterization of AKB-48 Metabolism, a Novel Synthetic Cannabinoid, Using Human Hepatocytes and High-Resolution Mass Spectrometry
The AAPS Journal, 2013Co-Authors: Adarsh S. Gandhi, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Mingshe Zhu, Hua-fen Liu, Marilyn A HuestisAbstract:Since the federal authorities scheduled the first synthetic cannabinoids, JWH-018 and JWH-073, new synthetic cannabinoids were robustly marketed. N -(1-Adamantyl)-1-pentylindazole-3-carboxamide (AKB-48), also known as APINACA, was recently observed in Japanese herbal smoking blends. The National Forensic Laboratory Information System registered 443 reports of AKB-48 cases in the USA from March 2010 to January 2013. In May 2013, the Drug Enforcement Administration listed AKB-48 as a Schedule I drug. Recently, AKB-48 was shown to have twice the CB_1 receptor binding affinity than CB_2. These pharmacological effects and the difficulty in detecting the parent compound in urine highlight the importance of metabolite identification for developing analytical methods for clinical and Forensic investigations. Using human hepatocytes and TripleTOF mass spectrometry, we identified 17 novel phase I and II AKB-48 metabolites, products of monohydroxylation, dihydroxylation, or trihydroxylation on the aliphatic adamantane ring or N -pentyl side chain. Glucuronide conjugation of some mono- and dihydroxylated metabolites also occurred. Oxidation and dihydroxylation on the adamantane ring and N -pentyl side chain formed a ketone. More metabolites were identified after 3 h of incubation than at 1 h. For the first time, we present a AKB-48 metabolic scheme obtained from human hepatocytes and high-resolution mass spectrometry. These data are needed to develop analytical methods to identify AKB-48 consumption in clinical and Forensic testing.
Ariane Wohlfarth - One of the best experts on this subject based on the ideXlab platform.
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distinguishing between cyclopropylfentanyl and crotonylfentanyl by methods commonly available in the Forensic Laboratory
Therapeutic Drug Monitoring, 2019Co-Authors: Ariane Wohlfarth, Marianne Skovskov Bergh, Inger Lise Bogen, Steven Ray Wilson, Ase Marit Leere OiestadAbstract:Background:The opioid analgesic fentanyl and its analogues pose a major health concern due to its high potency and the increasing number of overdose deaths worldwide. The analogues of fentanyl may differ in potency, toxicity, and legal status, and it is therefore important to develop analytical meth
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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
Clinical Chemistry, 2015Co-Authors: Xingxing Diao, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Marilyn A HuestisAbstract: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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First Characterization of AKB-48 Metabolism, a Novel Synthetic Cannabinoid, Using Human Hepatocytes and High-Resolution Mass Spectrometry
The AAPS Journal, 2013Co-Authors: Adarsh S. Gandhi, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Mingshe Zhu, Hua-fen Liu, Marilyn A HuestisAbstract:Since the federal authorities scheduled the first synthetic cannabinoids, JWH-018 and JWH-073, new synthetic cannabinoids were robustly marketed. N -(1-Adamantyl)-1-pentylindazole-3-carboxamide (AKB-48), also known as APINACA, was recently observed in Japanese herbal smoking blends. The National Forensic Laboratory Information System registered 443 reports of AKB-48 cases in the USA from March 2010 to January 2013. In May 2013, the Drug Enforcement Administration listed AKB-48 as a Schedule I drug. Recently, AKB-48 was shown to have twice the CB_1 receptor binding affinity than CB_2. These pharmacological effects and the difficulty in detecting the parent compound in urine highlight the importance of metabolite identification for developing analytical methods for clinical and Forensic investigations. Using human hepatocytes and TripleTOF mass spectrometry, we identified 17 novel phase I and II AKB-48 metabolites, products of monohydroxylation, dihydroxylation, or trihydroxylation on the aliphatic adamantane ring or N -pentyl side chain. Glucuronide conjugation of some mono- and dihydroxylated metabolites also occurred. Oxidation and dihydroxylation on the adamantane ring and N -pentyl side chain formed a ketone. More metabolites were identified after 3 h of incubation than at 1 h. For the first time, we present a AKB-48 metabolic scheme obtained from human hepatocytes and high-resolution mass spectrometry. These data are needed to develop analytical methods to identify AKB-48 consumption in clinical and Forensic testing.
Paul J Speaker - One of the best experts on this subject based on the ideXlab platform.
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an independent evaluation of Laboratory staffing needs launching the Forensic Laboratory workforce calculator
Forensic science international. Synergy, 2021Co-Authors: Paul J SpeakerAbstract:The 2019 NIJ Report to Congress on the needs of the Forensic science community [1] highlighted the staffing deficit of Forensic scientists by more than 900 positions. The Report emphasized the impact of the opioid crisis and the evolution of synthetic opioids on the demands for Forensic laboratories. The resource drain attributable to the opioid crisis has filtered into all other areas of investigation as laboratories divert limited resources from other uses to meet the high demand in drug chemistry and toxicology from opioid abuse. We introduce the Forensic Laboratory workforce calculator, a tool that any Forensic Laboratory may use to evaluate their current personnel allocation and estimate any under- or over-staffing to meet current or estimated caseloads. The Forensic Laboratory workforce calculator is available free to any Laboratory through the Forensic Technology Center of Excellence website.
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the jurisdictional return on investment from processing the backlog of untested sexual assault kits
Forensic Science International: Synergy, 2019Co-Authors: Paul J SpeakerAbstract:Abstract The economic problem for the Forensic Laboratory is a problem faced in all arenas; limited resources are available to address seemingly unlimited desires. This is as true for entities in the public sector as it is for any private concern. To assist decision-makers in the allocation of those scarce resources, we synthesize existing research on the benefits of additions to the DNA Database and the potential benefits from diverting resources to analysis of the backlog of sexual assault kits. We offer some guidance for the optimum use of limited resources, through the measurement of the return on investment (ROI) at the jurisdictional level (i.e., that is, the net benefits to society relative to the investment itself). These net benefits include those to survivors from a resolution to their assaults, the benefits to others from the prevention of repeated assaults from serial rapists, and the prevention of societal costs external to those directly victimized. Those external costs extend from the effects on friends and family to expenses for preventive measures to anyone aware of sexual assaults. Such metrics surrounding ROI will assist the public sector in the optimal allocation of scarce resources to the justice system by providing a measures of the marginal social welfare improvement from alternative allocations of these scarce resources in light of objectives of public sector entities. The analysis demonstrates that the societal return on investment from the testing of all sexual assault kits ranges from 9,874% to 64,529%, depending on the volume of activity for the Laboratory conducting the analysis. There are extreme economies of scale in effect that are suggestive of some policy alternatives.
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strategic management of Forensic Laboratory resources from project foresight metrics to the development of action plans
Forensic Science Policy & Management: An International Journal, 2011Co-Authors: Jonathan Newman, David D Dawley, Paul J SpeakerAbstract:Abstract The project FORESIGHT stated objectives begin with the development of metrics applicable to the activity of Forensic science laboratories. These metrics enable a Laboratory to assess how they fit within the Forensic science industry and offer a glance at the levels of performance that they might be able to achieve. FORESIGHT's mission goes on to state the intent for laboratories to use those measurements to “preserve what works, and change what does not” (Houck et al. 2009, p. 85). This paper addresses the strategic implications of those additional aspects of the FORESIGHT mandate with a view of the strategic planning process for a Forensic science Laboratory. The keys to the development of an ongoing strategic planning and execution process are outlined, and then the actions of one Laboratory, Ontario's Centre of Forensic Sciences, are examined to demonstrate the move from metrics to action. While there cannot yet be made a claim of “best practices,” this Canadian example offers some guidance to...
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benchmarking and budgeting techniques for improved Forensic Laboratory management
Forensic Science Policy & Management: An International Journal, 2010Co-Authors: Paul J Speaker, Scott A FlemingAbstract:Abstract Forensic laboratories are not immune from downturns in the worldwide economy. Recession and economic slowdowns, when coupled with the public's heightened sense of the capabilities of Forensic science, put stress on the effectiveness of Forensic laboratories. The resources available to Forensic laboratories are limited, and managers are under greater pressure to improve efficiency and effectiveness. To this end, the use of internal and external financial and accounting metrics to plan, control, evaluate, and communicate performance is examined. Using data from the QUADRUPOL and FORESIGHT studies, we illustrate the use of external benchmarking through a calculation of Laboratory return on investment and the internal development and use of a budget to enhance Laboratory performance in light of limited resources.
Karl B. Scheidweiler - One of the best experts on this subject based on the ideXlab platform.
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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
Clinical Chemistry, 2015Co-Authors: Xingxing Diao, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Marilyn A HuestisAbstract: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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First Characterization of AKB-48 Metabolism, a Novel Synthetic Cannabinoid, Using Human Hepatocytes and High-Resolution Mass Spectrometry
The AAPS Journal, 2013Co-Authors: Adarsh S. Gandhi, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Mingshe Zhu, Hua-fen Liu, Marilyn A HuestisAbstract:Since the federal authorities scheduled the first synthetic cannabinoids, JWH-018 and JWH-073, new synthetic cannabinoids were robustly marketed. N -(1-Adamantyl)-1-pentylindazole-3-carboxamide (AKB-48), also known as APINACA, was recently observed in Japanese herbal smoking blends. The National Forensic Laboratory Information System registered 443 reports of AKB-48 cases in the USA from March 2010 to January 2013. In May 2013, the Drug Enforcement Administration listed AKB-48 as a Schedule I drug. Recently, AKB-48 was shown to have twice the CB_1 receptor binding affinity than CB_2. These pharmacological effects and the difficulty in detecting the parent compound in urine highlight the importance of metabolite identification for developing analytical methods for clinical and Forensic investigations. Using human hepatocytes and TripleTOF mass spectrometry, we identified 17 novel phase I and II AKB-48 metabolites, products of monohydroxylation, dihydroxylation, or trihydroxylation on the aliphatic adamantane ring or N -pentyl side chain. Glucuronide conjugation of some mono- and dihydroxylated metabolites also occurred. Oxidation and dihydroxylation on the adamantane ring and N -pentyl side chain formed a ketone. More metabolites were identified after 3 h of incubation than at 1 h. For the first time, we present a AKB-48 metabolic scheme obtained from human hepatocytes and high-resolution mass spectrometry. These data are needed to develop analytical methods to identify AKB-48 consumption in clinical and Forensic testing.
Shaokun Pang - One of the best experts on this subject based on the ideXlab platform.
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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
Clinical Chemistry, 2015Co-Authors: Xingxing Diao, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Marilyn A HuestisAbstract: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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First Characterization of AKB-48 Metabolism, a Novel Synthetic Cannabinoid, Using Human Hepatocytes and High-Resolution Mass Spectrometry
The AAPS Journal, 2013Co-Authors: Adarsh S. Gandhi, Karl B. Scheidweiler, Ariane Wohlfarth, Shaokun Pang, Mingshe Zhu, Hua-fen Liu, Marilyn A HuestisAbstract:Since the federal authorities scheduled the first synthetic cannabinoids, JWH-018 and JWH-073, new synthetic cannabinoids were robustly marketed. N -(1-Adamantyl)-1-pentylindazole-3-carboxamide (AKB-48), also known as APINACA, was recently observed in Japanese herbal smoking blends. The National Forensic Laboratory Information System registered 443 reports of AKB-48 cases in the USA from March 2010 to January 2013. In May 2013, the Drug Enforcement Administration listed AKB-48 as a Schedule I drug. Recently, AKB-48 was shown to have twice the CB_1 receptor binding affinity than CB_2. These pharmacological effects and the difficulty in detecting the parent compound in urine highlight the importance of metabolite identification for developing analytical methods for clinical and Forensic investigations. Using human hepatocytes and TripleTOF mass spectrometry, we identified 17 novel phase I and II AKB-48 metabolites, products of monohydroxylation, dihydroxylation, or trihydroxylation on the aliphatic adamantane ring or N -pentyl side chain. Glucuronide conjugation of some mono- and dihydroxylated metabolites also occurred. Oxidation and dihydroxylation on the adamantane ring and N -pentyl side chain formed a ketone. More metabolites were identified after 3 h of incubation than at 1 h. For the first time, we present a AKB-48 metabolic scheme obtained from human hepatocytes and high-resolution mass spectrometry. These data are needed to develop analytical methods to identify AKB-48 consumption in clinical and Forensic testing.