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Recommended Methods for the Identification and Analysis of Fentanyl and Its Analogues in Biological Specimens
Recommended methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Recommended Methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES UNITED NATIONS Vienna, 2017 Note Operating and experimental conditions are reproduced from the original reference materials, including unpublished methods, validated and used in selected national laboratories as per the list of references. A number of alternative conditions and substitution of named commercial products may provide comparable results in many cases. However, any modification has to be validated before it is integrated into laboratory routines. ST/NAR/53 Original language: English © United Nations, November 2017. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Mention of names of firms and commercial products does not imply the endorse- ment of the United Nations. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. Acknowledgements The Laboratory and Scientific Section of the UNODC (LSS, headed by Dr. Justice Tettey) wishes to express its appreciation and thanks to Dr. Barry Logan, Center for Forensic Science Research and Education, at the Fredric Rieders Family Founda- tion and NMS Labs, United States; Amanda L.A. -
Infographics About Synthetic Opioids
UNODC LEADING THE INTERGRATED GLOBAL RESPONSE TO THE OPIOID CRISIS P I L L A R 1 P I L L A R 2 P I L L A R 3 P I L L A R 4 P I L L A R 5 I N T E R N A T I O N A L L A W S T R E N G T H E N I N G C O U N T E R E A R L Y W A R N I N G A N D R A T I O N A L P R E S C R I B I N G A N D S T R E N G T H E N I N G A N D S U P P O R T I N G E N F O R C E M E N T O P E R A T I O N S N A R C O T I C C A P A C I T Y A N D T R E N D A N A L Y S I S A C C E S S T O O P I O I D S P R E V E N T I O N A N D T R E A T M E N T T O D I S R U P T T R A F F I C K I N G I N T E R N A T I O N A L C O O P E R A T I O N IDENTIFYING THE MOST PREVELANT, PERSISTANT AND HARMFUL SYNTHETIC OPIOIDS U N O D C 282 90 E A R L Y TOXICOLOGY COLLABORATING IN COUNTRIES W A R N I N G INFORMED THREATS LABORATORIES A D V I S O R Y ASSESSMENTS PHARMACOLOGICAL INFORMATION L A B O R A T O R I E S A N D D A T A P O I N T S L A B O R A T O R I E S D A T A P O I N T S G L O B A L S M A R T U P D A T E S 21,400+ 120 DATA POINTS FROM COUNTRIES SYNTHETIC SEDATIVE 74 OPIOIDS HYPNOTICS REPORTED MIRRORING TO UNODC SYNTHETIC E A R L Y OPIOID TRENDS W A R N I N G A D V I S O R Y B Y 2019 131% IN THE LAST * * 3 Y E A R S Note: * 2019 data collection not finalized LIST OF SYNTHETIC OPIOIDS REPORTED TO THE UNODC EWA FROM 2009-2019 S C H E D U L E D 2-Fluorofentanyl Furanylfentanyl 4-Fluorobutyrfentanyl Methoxyacetylfentanyl 4-Fluoroisobutyrfentanyl MT-45 S C H E D U L E I Acrylfentanyl Ocfentanil ( 1 9 6 1 ) AH-7921 Tetrahydrofuranylfentanyl Butyrfentanyl U-47700 S C H E D U L E I & I V Cyclopropylfentanyl -
ANNEX I. FENTANYL-RELATED Substancesa with NO CURRENTLY KNOWN LEGITIMATE USES
ANNEX I. FENTANYL-RELATED SUBSTANCESa WITH NO CURRENTLY KNOWN LEGITIMATE USES CAS No. d Intl No.* Uses b Common Substance Name Other/ Alternative Substance Name(s) c Abbreviations CAS No.d (HCl) Ctrl.e 1 Unknown 2,2'-difluorofentanyl N-(1-(2-fluorophenethyl)piperidin-4-yl)-N-(2-fluorophenyl)propionamide; 2'-ortho-difluorofentanyl; 2'-fluoro ortho- fluorofentanyl 2 Unknown 2-fluoro butyrfentanyl N-(2-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)butyramide; N-(2-fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]- 2-FBF; 2F-BF; o- 2163847-76-3 butanamide (IUPAC); 2-fluoro butyrylfentanyl; ortho-fluorobutyryl fentanyl FBF 3 No Known 2-fluorofentanyl ortho-fluorofentanyl; N-(2-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)propionamide 2-FF; o-FF 910616-29-4 1961/I Uses 4 Unknown 2-furanylethyl fentanyl N-[1-[2-(2-furanyl)ethyl]-4-piperidinyl]-N-phenyl-propanamide 802544-02-1 1443-49-8 5 Unknown 2-isopropylfuranyl fentanyl 2-isopropyl furanyl fentanyl; ortho-isopropyl furanyl fentanyl; N-(2-isopropylphenyl)-N-(1-phenethylpiperidin-4-yl)furan- 2-isopropyl Fu-F 2-carboxamide; 2-Furanylfentanyl ortho-2-isopropylphenyl analogue 6 Unknown 2-methoxy furanyl fentanyl N-(2-methoxyphenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-2-furancarboxamide; 2-Furanylfentanyl ortho-2- 2-methoxy FuF; 2- 101343-50-4 methoxyphenyl analogue; ortho-methoxy furanyl fentanyl Meo-FuF 7 Unknown 2-methyl furanyl fentanyl N-(1-phenethylpiperidin-4-yl)-N-(o-tolyl)furan-2-carboxamide 2-methyl FuF 8 Unknown 3-allyl fentanyl N-phenyl-N-[1-(2-phenylethyl)-3-(prop-2-en-1-yl)piperidin-4-yl]propanamide -
Nicole T. Labor, Do Nicole T
UPDATES IN THE OPIOID EPIDEMIC NICOLE T. LABOR, DO NICOLE T. LABOR, DO • Board Certified in Familly Medicine. • Board certified in Addiction medicine • Associate Medical Director of Addiction Medicine, Summa Physicians Inc., Akron, OH • Medical Director Esper Treatment Center, Erie, PA • Chief Medical Officer, Interval Brotherhood Home, Akron, OH • Director of Medication Assisted Treatment, STEPs, Wooster, OH • Associate Clinical Professor of psychiatry and family and community medicine, NEOMED • Director of Addiction Medicine Fellowship, Summa LEARNING OBJECTIVES • 1. Discuss the current trends with the opioid epidemic • 2. Discuss the current issues with fentanyl, fentanyl analogs, carfentanil and U-47700. • 3. Discuss treatment options • 4. Discuss when to refer to Addiction Medicine. WHY AN EPIDEMIC? • Epidemic: • The occurrence of more cases of a disease than would be expected in a community or region during a given time period. • A sudden severe outbreak of a disease. • From the Greek "epi-", "upon" + "demos", "people or population" = "epidemos" = "upon the population.“ Source: MedicineNet: http://www.medicinenet.com/script/main/ OTHER EPIDEMICS • Crack cocaine: In 1985, cocaine-related hospital emergencies rose by 12 percent, from 23,500 to 26,300. In 1986, these incidents increased 110 percent, from 26,300 to 55,200. Between 1984 and 1987, cocaine incidents increased to 94,000. • Methamphetamine: The Combat Methamphetamine Epidemic Act of 2005 (CMEA) is federal legislation enacted in the United States on March 9, 2006, to regulate, among other things, retail over-the-counter sales of following products because of their use in the manufacture of illegal drugs: ephedrine, pseudephedrine, phenapropanolamine • Bath Salts: In October 2011, the DEA used its administrative powers to institute an emergency but temporary one-year ban on the three basic bath-salt chemicals, declaring them Schedule 1 substances. -
Misuse of Fentanyl and Fentanyl Analogues
ACMD Advisory Council on the Misuse of Drugs ACMD Chair: Dr Owen Bowden-Jones ACMD NPS Committee Secretary: Imogen McHarg 4th Floor (NE), Peel Building 2 Marsham Street London SW1P 4DF [email protected] Rt. Hon. Priti Patel MP Home Secretary 2 Marsham Street London SW1P 4DF Friday, 3 January 2020 Dear Home Secretary, Re: ACMD Report – Misuse of Fentanyl and Fentanyl Analogues In July 2017 the then-Home Secretary commissioned the Advisory Council on the Misuse of Drugs (ACMD) to consider fentanyl and fentanyl analogues following the publication of the Drug Strategy 2017. Prompted by concerns over increasing drug-related deaths rates and growing evidence from law enforcement agencies of fentanyl entering European drug markets, this commission sought advice from the ACMD on the number and nature of known fentanyl analogues - and their known and likely risk factors. This report includes: a literature review on the pharmacology and toxic effects of fentanyl and related analogues; details of the misuse potential of both pharmaceutical and illicitly manufactured fentanyl compounds, and, a summary of the associated harms as documented internationally and in the UK. The Misuse of Drugs Act 1971 already contains a generic definition for fentanyls which has proved to be robust in bringing the majority of fentanyl-related analogues under legal control. Despite this, the rates of registered deaths involving fentanyl variants in the UK have increased over the past decade, with deaths likely to be under-represented, since sufficiently detailed forensic analyses are not always carried out. 1 Therefore, it can be concluded that fentanyl and fentanyl-analogues present a significant ongoing risk to UK public health. -
Metabolic Pathways and Potencies of New Fentanyl Analogs
fphar-10-00238 April 5, 2019 Time: 19:11 # 1 REVIEW published: 05 April 2019 doi: 10.3389/fphar.2019.00238 Metabolic Pathways and Potencies of New Fentanyl Analogs Maurice Wilde1,2, Simona Pichini3, Roberta Pacifici3, Adriano Tagliabracci4, Francesco Paolo Busardò4*, Volker Auwärter1 and Renata Solimini3 1 Department of Forensic Toxicology, Institute of Forensic Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany, 2 Hermann Staudinger Graduate School, University of Freiburg, Freiburg im Breisgau, Germany, 3 National Centre on Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy, 4 Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence SBSP, Università Politecnica delle Marche, Ancona, Italy Up to now, little is known about the metabolic pathways of new fentanyl analogs that have recently emerged on the drug markets worldwide with high potential for producing addiction and severe adverse effects including coma and death. For some of the compounds, limited information on the metabolism has been published, however, for others so far no information is available. Considering the well characterized metabolism of the pharmaceutically used opioid fentanyl and the so far available data, the metabolism of the new fentanyl analogs can be anticipated to generally involve reactions like hydrolysis, hydroxylation (and further oxidation steps), N- and O-dealkylation and Edited by: O-methylation. Furthermore, phase II metabolic reactions can be expected comprising Luis F. Callado, University of the Basque Country, glucuronide or sulfate conjugate formation. When analyzing blood and urine samples Spain of acute intoxication cases or fatalities, the presence of metabolites can be crucial Reviewed by: for confirmation of the uptake of such compounds and further interpretation. -
Amber ALERT the Use of the Clearnet and Social Media for the Advertising and Sale of Fentanyl Analogues
OFFICIAL Amber ALERT The use of the clearnet and social media for the advertising and sale of fentanyl analogues Date: July 2019 Reference: 0556 - DICE This Amber Alert is issued by the United Kingdom’s National Crime Agency (NCA). It is based on assessed intelligence and warns of dangers and threats from serious organised criminality. It is devised with the aim of bringing about preventative or remedial action. We recommend you use this Alert to complement existing knowledge and support ongoing improvements to your business processes and procedures. OFFICIAL The use of the clearnet1 and social media for the advertising and sale of fentanyl analogues Overview Criminal groups and individuals are known to use social media platforms as well as the wider internet for example websites, forums, blogs, business to business portals etc to advertise and sell a wide range of drugs that are designated as illegal and graded for criminal law purposes as Class A, B and C Controlled drugs. This report focuses on the sale of Class A fentanyl analogues and considers the following: What are fentanyl analogues and why are they so dangerous? i. Illicit use of fentanyl ii. Why fentanyl analogues? iii. The legal status of fentanyl analogues iv. Impact on the UK by illicit fentanyl analogues The supply of fentanyl analogues online i. Who can assist us and how can companies help? ii. Keywords and known issues What we would like you to do The information is being shared by the NCA to help develop understanding of the threat posed by the clearnet advertising and sale of fentanyl analogues. -
Opioid Crisis
GLOBAL SMART UPDATE THE GROWING EN COMPLEXITY OF THE OPIOID CRISIS VOLUME 24 October 2020 GLOBAL SMART UPDATE About the SMART Update Content A. INTRODUCTION 3 Synthetic drugs constitute one of the most significant drug problems worldwide. Along with synthetic drugs, the emergence The multi-faceted opioid crisis – 3 of the new psychoactive substances (NPS) market over the last What, why and how? years has become a policy challenge and a major international Substances with opioid effects are one of 4 concern. A growing interplay between these new substances the fastest growing groups of NPS and traditional illicit drug markets is being observed, and the synthetic drugs market continues to evolve rapidly. The global tragedy of unnecessary pain 4 and suffering – insufficient access to The Global SMART Updates (GSU)* are biannual publications internationally controlled opioids for medical use of the UNODC Global Synthetics Monitoring: Analyses, Reporting and Trends (SMART) Programme, implemented by the UNODC B. INTERNATIONAL AND NATIONAL POLICY 5 Laboratory and Scientific Section. The GSU is published in RESPONSES TO THE OPIOID CRISIS English, Spanish and Russian. The Global SMART Programme enhances the capacity of Member States in priority regions to C. THE GROWING COMPLEXITY OF THE 6 generate, manage, analyse, report and use synthetic drugs OPIOID CRISIS – EMERGENCE OF A NEW information to design effective policy and programme interventions. GENERATION OF SYNTHETIC OPIOIDS The main products and services of the Global SMART Programme Trends in non-fentanyl related synthetic opioids 6 include capacity building workshops, online drug data collection, national, regional and global assessment reports, and the Failed pharmaceutical opioids: from potential 8 UNODC Early Warning Advisory (EWA) on NPS. -
Metabolic Pathways and Potencies of New Fentanyl Analogs
fphar-10-00238 April 4, 2019 Time: 14:46 # 1 REVIEW published: 05 April 2019 doi: 10.3389/fphar.2019.00238 Metabolic Pathways and Potencies of New Fentanyl Analogs Maurice Wilde1,2, Simona Pichini3, Roberta Pacifici3, Adriano Tagliabracci4, Francesco Paolo Busardò4*, Volker Auwärter1 and Renata Solimini3 1 Department of Forensic Toxicology, Institute of Forensic Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany, 2 Hermann Staudinger Graduate School, University of Freiburg, Freiburg im Breisgau, Germany, 3 National Centre on Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy, 4 Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence SBSP, Università Politecnica delle Marche, Ancona, Italy Up to now, little is known about the metabolic pathways of new fentanyl analogs that have recently emerged on the drug markets worldwide with high potential for producing addiction and severe adverse effects including coma and death. For some of the compounds, limited information on the metabolism has been published, however, for others so far no information is available. Considering the well characterized metabolism of the pharmaceutically used opioid fentanyl and the so far available data, the metabolism of the new fentanyl analogs can be anticipated to generally involve reactions like hydrolysis, hydroxylation (and further oxidation steps), N- and O-dealkylation and Edited by: O-methylation. Furthermore, phase II metabolic reactions can be expected comprising Luis F. Callado, University of the Basque Country, glucuronide or sulfate conjugate formation. When analyzing blood and urine samples Spain of acute intoxication cases or fatalities, the presence of metabolites can be crucial Reviewed by: for confirmation of the uptake of such compounds and further interpretation. -
Prevalence of Fentanyl and Its Analogs in Court-Ordered Mandatory Drug Testing in Hair 2020 Internship Showcase
Prevalence of Fentanyl and Its Analogs in Court-Ordered Mandatory Drug Testing in Hair 2020 Internship Showcase Jessica Bunn Virginia Commonwealth [email protected] www.rti.org RTI International is a trade name of Research Triangle Institute. RTI and the RTI logo are U.S. registered trademarks of Research Triangle Institute. Fentanyl Laboratory Drug Seizures of Fentanyl Top five drug 60000 seizures in 2018: 50000 1. Methamphetamine 40000 2. Cannabis/THC 30000 3. Cocaine 4. Heroin 20000 5. Fentanyl 10000 0 2 (Drug Enforcement Administration, 2019) Current Methods for Analysis o Current methods focus on heroin, codeine, and morphine targets. o Historically, fentanyl exposure comes from fentanyl-containing heroin. o Now, fentanyl and its analogs are used on their own. o Many samples potentially could be falsely reported as negative if fentanyl and its analogs are not included in the testing. How many fentanyl and analog users are being missed? 3 Fentanyl and Analog Use • Because of changes in legal status, fentanyl analogs often change in popularity. • These changes increase the difficulty for analysis because new analogs are constantly being developed. What analogs are new and popular, so testing is accurate? 500 Prominent Opioids 400 300 200 100 0 Acetyl Fentanyl 2-Furanyl Fentanyl 4-FiBF Carfentanil 2016 2017 2018 2019 4 (Special Testing and Research Laboratory, n.d.b) Acetylfentanyl Fentanyl Analog Trends 4-ANPP Carfentanil *Furanylfentanyl 2-furanylfentanyl Valerylfentanyl Acetylfentanyl 4-FiBF *U-47700 U-47700 butyrylfentanyl 4-ANPP -
Toxicological Time Travel
The author(s) shown below used Federal funding provided by the U.S. Department of Justice to prepare the following resource: Document Title: Toxicological Time Travel: Retrospective Datamining of Analytical Time-of-Flight Mass Spectrometry (TOFMS) Data for Evaluating the Rise and Fall of Novel Opioid and Fentanyl Analog Use in the United States Author(s): Amanda LA Mohr, MSFS, D-ABFT-FT, Judith Rodriguez Salas, MS, Barry K Logan, Ph.D., F-ABFT Document Number: 255883 Date Received: December 2020 Award Number: 2017-DN-BX-0169 This resource has not been published by the U.S. Department of Justice. This resource is being made publically available through the Office of Justice Programs’ National Criminal Justice Reference Service. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Title: Toxicological Time Travel: Retrospective Datamining of Analytical Time-of-Flight Mass Spectrometry (TOFMS) Data for Evaluating the Rise and Fall of Novel Opioid and Fentanyl Analog Use in the United States Authors: Amanda LA Mohr, MSFS, D-ABFT-FT, Judith Rodriguez Salas, MS, and Barry K Logan, PhD, F-ABFT Organization: Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, PA, USA Award Number: 2017-DN-BX-0169 This resource was prepared by the author(s) using Federal funds provided by the U.S. Department of Justice. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. -
Methoxyacetylfentanyl
RISK ASSESSMENTS 30 ISSN 1725-4493 Methoxyacetylfentanyl Report on the risk assessment of 2-methoxy- N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl] acetamide in the framework of the Council Decision on new psychoactive substances About this series EMCDDA Risk Assessments are publications examining the health and social risks of individual new psychoactive substances. The Risk Assessment Report consists of an analysis of the scientific and law enforcement information available on the new psychoactive substance under scrutiny and the implications of placing it under control. It is the outcome of a meeting convened under the auspices of the EMCDDA Scientific Committee. This process is part of a three-step procedure involving information exchange/early warning, risk assessment and decision-making in the framework of Council Decision 2005/387/JHA. RISK ASSESSMENT I Methoxyacetylfentanyl Contents Foreword ……………………………………………………………………………………………….……….3 EMCDDA actions on monitoring and responding to new drugs …………………...………………………4 EMCDDA‒Europol Joint Report on 2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide (methoxyacetylfentanyl): a summary……………………………………………………………….…………5 Risk Assessment Report of a new psychoactive substance: 2-methoxy-N-phenyl-N-[1-(2- phenylethyl)piperidin-4-yl]acetamide (methoxyacetylfentanyl)……………………………………………..6 Annex 1: Technical report on 2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]acetamide (methoxyacetylfentanyl) ………………………………………………………………………………………25 Participants of the risk assessment meeting………………………………………………………………..55 Acknowledgements The EMCDDA would like to thank the following for their contribution in producing this publication: . the members of the extended Scientific Committee of the EMCDDA; the advisers to the Scientific Committee and the invited external experts who took part in the risk assessment meeting; .