Carfentanil Through the Years: A Look at Data From 2016-2024
By Stuart Kurtz, D-ABFT-FT
Last month, Axis was represented at the Midwest Association for Toxicology and Therapeutic Drug Monitoring’s annual meeting. Toxicologist Stuart Kurtz gave a presentation on the lab’s detections of carfentanil since Axis started testing for it in 2016. The focus of this presentation was on the increase in detections Axis noticed in 2023 and where Axis has been detecting carfentanil. This data is only representative of casework Axis has done.
In a previous blog post, we wrote about a minor surge in detections in early to mid-2023. Due to the potent nature of carfentanil and implications for public health concerns, we wanted to refresh everyone’s minds that this drug can still be found in casework.
*2024 is evaluated for 01/01/2024-04/26/2024
In the last month and a half since we looked at our 2024 data, Axis now has 61 detections for carfentanil. This puts 2024 on pace to be the 2nd highest year for detections since Axis started testing for it. It should be noted that prior to 2020, carfentanil was not included in Axis’ routine screening. It’s now a part of our 70510: Comprehensive Panel with Analyte Assurance or as part of the 13810: Designer Opioids Panel.
While carfentanil detections represent a small percentage of total casework, ~1% in 2024 so far, its recent increase in detections was noticed in June 2023. Axis had 4 cases that month with a 5th case at the end of May. At this point, Axis’ toxicologists began to monitor the increase in detections to see if it continued. The number of detections held steady until a large increase November 2023. The main areas where this occurred were Florida and Kentucky. In a meeting with other members of Florida toxicology labs, they mentioned that they also saw an increase in detections of carfentanil around that time. In January 2024, detections in Florida decreased almost to zero while Kentucky remained steady. Kentucky continues to be the area with the most detections in 2024. Other states such as Indiana, Ohio, and Kansas are also seeing detections in 2024.
*April 2024 is evaluated through 04/26/2024.
As always, please reach out to Axis’ toxicologists with any questions regarding this data or help interpreting your results. You can email us at [email protected] or call us at 317-759-4869 option 3.
- Published in Drug Classes, General
Quantitative vs. Qualitative Testing
By Kevin Shanks, M.S., D-ABFT-FT
To quantify or not? That is the question. If you regularly read forensic toxicology reports, then you know laboratory tests can be qualitative or quantitative. Qualitative tests only provide a positive/present or negative result. Quantitative tests are tests that have a numerical result. So, why do we report some tests as qualitative and some as quantitative? There are a couple of different answers that resolve the question.
Firstly, in forensic toxicology, blood is the gold standard when it comes to analytical testing as blood gives a snapshot of drug exposure and potential toxicity of circulating drugs in the window of a few minutes to several hours. Studies compile reference ranges or sets of blood drug or metabolite concentrations used as a guideline for interpreting results. These can normally be classified as therapeutic, toxic, and fatal ranges. Therapeutic blood concentration is the concentration of a drug or its active metabolite which is present in the blood following a therapeutic dosage of the drug. Most therapeutic ranges originate from data acquired during pharmaceutical medication human clinical trials or controlled dosing drug studies. Toxic blood concentration is the concentration of a drug, or its active metabolite, present in the blood that is associated with serious adverse symptoms. Fatal blood concentration is the concentration of a drug, or its active metabolite, present in the blood that has been reported to cause fatality or is so far above reported therapeutic or toxic concentrations, that one may judge it might cause fatality. Alternative matrices such as liver and brain tissue have very limited reference data available, and the availability is typically relegated to the classical drugs of abuse. Urine, on the other hand, gives a much wider window of drug detection – usually on the order of 1-5 days – but any drug or metabolite that is detected in urine is not imparting a pharmacological effect on the body. As urine is an excretory product, quantitative results do not and cannot correlate to or be associated with impairment, toxicity, or fatality.
For those drugs that have clinical human trial data, for those drugs that have controlled dosing studies, and for those drugs that have established toxic and lethal reference ranges, quantitative testing is applicable. A forensic toxicologist can use the data and the established blood concentration ranges as a guide to aid in interpreting the analytical result and potentially come to an opinion on the role of a substance in an incident such as driving while impaired or the cause of death of an individual. On the other hand, alternative matrices such as tissue or urine may be reported as qualitative only due to the limited amount of reference data available or the nature of the specimen being a waste product.
What about those substances that are new to the drug scene? What about those new street drugs or novel psychoactive substances (NPS)? We do not have human clinical trial data for these substances. We do not have controlled dosing studies for these substances. For some newly established compounds on the street, we may not even know their true pharmacological action in the body. What receptors do they bind to? How tightly do they bind to the receptor? What metabolites does the body produce? Are those metabolites active or inactive? What effects does the drug elicit? In a controlled setting, what blood concentrations are typically observed? Are those blood concentrations correlated to or with a specific effect or behavior or toxicity?
There is a paucity of information when it comes to new drugs as well as alternative matrices. And for this reason, many laboratories will choose to report qualitative results only. When there is a lack of this quantitative reference data, the mere presence of the drug is the important part in the interpretation of the toxicology results.
A second reason why a laboratory may choose to report qualitative results over quantitative results is two-fold – the extensive work and costs that goes in to developing and validating the analytical method to determine the result in the lab in combination with the rapidly changing illicit drug market.
NPS such as fentanyl analogs, nitazene opioids, synthetic cannabinoids, and designer benzodiazepines ebb and flow as time goes on. They can appear and disappear rapidly over weeks to months. By the time the analytical method is validated and on-boarded to the laboratory, there is a good chance that the drugs that were prevalent on the market are no longer out there and have been replaced by other new drugs not in the newly updated method.
As an example, for a while around 2015-2020, synthetic cannabinoids were prevalent in the USA and the street drug market was very rapidly changing. Compounds were emerging on the street, becoming prevalent, and then disappearing from the market within approximately a 3–6-month time span. In the span of a year or two, there were 10-20 new synthetic cannabinoids on the street. To either create a new quantitative test for these newly emerged substances or update a current test to include these new compounds, the development and validation process would take approximately 3-6 months. By the time the quantitative method was validated and approved for use in the laboratory, the entire drug scene on the street had changed and the new method was outdated. By validation protocols, qualitative tests are much quicker to validate than quantitative tests. So, as a forensic toxicology laboratory aiming to produce relevant (in time and scope) toxicology results in the aid of medical-legal investigations, it makes sense to develop qualitative tests for those newly emerged compounds.
Ultimately, whether it is a qualitative test or a quantitative analysis – the interpretation of results hinges on the context and circumstances of the case. Axis Forensic Toxicology understands that one should never practice toxicology in a vacuum, and we are here to help with interpretation of the relevant toxicology in your casework. If you have any questions or concerns regarding a substance’s reference range or its role in your medical-legal investigation, please reach out to our subject matter experts at [email protected].
References
Guidelines for the Interpretation of Analytical Toxicology Results. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages xxx-xlii. (2020).
Pharmacokinetics and Pharmacodynamics. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. American Association for Clinical Chemistry (AACC). 2017. 77-93.
Introduction to Forensic Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 1-12. (2008).
Postmortem Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 191-218. (2008).
Postmortem Forensic Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 3-14. (2017).
Reference Ranges. Axis Forensic Toxicology Blog. https://axisfortox.com/reference-ranges/ (2022).
- Published in Drug Classes
Axis Forensic Toxicology Announces Retirement of Chief Toxicologist and Welcomes New Chief Toxicologist
Axis Forensic Toxicology is proud to announce the retirement of Dr. George S. Behonick, Ph.D., F-ABFT, effective July 4, 2024. After four decades of laboratory and toxicology work including 15 years of dedicated service and exceptional leadership of Axis Forensic Toxicology, Dr. Behonick will be stepping down from his role as Lab Director and Chief Toxicologist. Throughout his tenure, Dr. Behonick has made invaluable contributions to the field of forensic toxicology, including testifying in over 100 court cases and depositions in 13 federal courts and 22 states. Dr. Behonick is the author or co-author of twenty peer-reviewed publications, over forty abstracts for poster and/or oral presentations, and several technical notes within the field of forensic toxicology. Earlier in his career, he served in scientific leadership roles with the Commonwealth of Massachusetts Office of the Chief Medical Examiner and the Commonwealth of Virginia’s Division of Forensic Science. Prior to Dr. Behonick’s toxicology education and career, he served 10 years as a decorated Officer in the United States Armey.
In light of this transition, Axis is thrilled to welcome Dr. Laureen J. Marinetti, Ph.D., F-ABFT, as the incoming Laboratory Director and Chief Toxicologist. Dr. Marinetti brings a wealth of experience and expertise in the field of forensic toxicology with over 30 years of experience in human performance and postmortem forensic toxicology in the areas of oral and written expert opinion testimony, drug interpretation, method development, quality assurance and control, laboratory accreditation and drug abuse demographics. Dr. Marinetti is a nationally recognized lecturer and expert witness in analytical and interpretive forensic toxicology and pharmacology and is also board certified by the American Board of Forensic Toxicology. She has authored several peer reviewed publications and book chapters in forensic toxicology. Dr. Marinetti’s leadership will undoubtedly propel Axis to new heights of excellence in forensic science. Dr. Marinetti will begin releasing cases the week of April 15th and assume the role of Lab Director effective June 1, 2024.
“We extend our heartfelt gratitude to Dr. Behonick for his years of dedicated service and outstanding contributions to Axis,” said Phil Roberts, Chief Executive Officer of Axis Forensic Toxicology. “We also warmly welcome Dr. Marinetti to our team and look forward to the innovative ideas and insights she will bring to our laboratory.”
Axis will be engaging its clients in this transition to celebrate Dr. Behonick and welcome Dr. Marinetti. Further details regarding these events will be shared at a later date.
Inquiries, well-wishes, or requests for further information may be directed to [email protected].
- Published in Announcements
Change to PRESENT Reporting
In the spirit of continuous improvement, we’d like to make you aware of a change that you will see on final toxicology reports beginning April 15th, 2024. Currently, when the qualitative result of “PRESENT” appears on a final toxicology report, it appears in black lettering as in the image below:
Beginning on April 15th, 2024 a qualitative result of “PRESENT” will appear in red lettering as in the image below, which is consistent with the appearance of a “POSITIVE” report.
This change has been made to clearly distinguish these results from those that are “Negative”. Our hope is that this change provides more clarity regarding results that indicate the presence of a particular compound vs. results that indicate no presence.
If you have any questions, please contact us at [email protected].
We look forward to serving you.
Sincerely,
Matt Zollman
Director of Operations & Product Management
- Published in Announcements
Comprehensive Panel & Novel Substance Expansion
Dear Valued Client,
In the spirit of continuous improvement and to provide the most relevant testing possible, we’re announcing a host of changes to our panels beginning on January 22nd, 2024. The changes are briefly outlined below:
Additionally as a reminder, analytes added to Designer Panels (including Order Codes 13610, 13710, 13810 and 13910 referenced above) are included as part of Order Code 70510: Comprehensive Panel with Analyte Assurance™.
If you have any questions regarding this change please do not hesitate to contact Lab Client Support at [email protected] to connect quickly to one of our Client Support Specialists.
We look forward to serving you.
Sincerely,
Matt Zollman
Director of Operations & Product Management
- Published in Announcements
Axis Offers Training Opportunities for Forensic Pathology Medicine Fellows
By Kevin G. Shanks, M.S., D-ABFT-FT
Axis Forensic Toxicology prides itself in its ability and willingness to provide continuing education and training for our forensic toxicology clients. One of these educational avenues is the Axis forensic medicine fellow training rotation program.
In this weeklong virtual training program, a Forensic Medicine Fellow will be introduced to the set-up and operation of the modern postmortem forensic toxicology laboratory, alongside descriptions of the analytical instrumentation and analytical methods employed by the laboratory. Board certified forensic toxicologists will discuss the importance of toxicology specimen collection and present a survey of the major illicit and pharmaceutical drugs (e.g. ethanol, cocaine, methamphetamine, MDMA, heroin, fentanyl, and prescription opioids) with respect to mechanisms of actions, their detection, and their relevance to cause of death determination. Novel psychoactive substances (NPS), to include designer benzodiazepines, synthetic cannabinoids, substituted cathinones, fentanyl analogs, nitazene derivatives, xylazine, and mitragynine (kratom) are also discussed in depth.
The forensic toxicology forensic medicine fellow training rotation instills the Fellow with confidence in interpreting the significance of toxicological findings with respect to cause and manner of death classification. Peer reviewed scientific references provided to the Fellow lay a foundation for a body of knowledge that may aid in the resolution of drug-related deaths by the forensic pathologist. One-on-one toxicology case review with a forensic toxicologist surveying completed cases by the laboratory will be undertaken and is intended to give the Fellow an overview of how a “toxicology pending conference” is conducted between forensic pathologists and forensic toxicologists.
If you are a forensic pathology fellow or a pathologist who directs forensic pathology fellows and are interested in learning more about this training opportunity, please reach out to Axis Forensic Toxicology’s toxicologists at [email protected] or call us on the phone at (317) 759 – 4869, Option 1.
- Published in General
Comprehensive Panel and Directed Fentanyl Changes
Dear Valued Client,
Beginning with orders submitted January 22nd, 2024, 4-ANPP will be part of Axis’ 70510: Comprehensive Panel w/ Analyte Assurance™ as a screened and automatically reflexed analyte. What this means in terms of practical application for clients is that you will no longer receive Analyte Assurance notifications regarding 4-ANPP, but rather will receive a final qualitatively confirmed result, at no additional charge, as part of the 70510: Comprehensive Panel w/ Analyte Assurance™.
In addition to this change reflected in the 70510: Comprehensive Panel w/ Analyte Assurance™, directed testing for 4-ANPP will be moved from the 13810: Designer Opioids Panel to the 40410: Fentanyl and Metabolites Order Code.
If you have any questions regarding this change please do not hesitate to contact Lab Client Support at [email protected] to connect quickly to one of our Client Support Specialists.
We look forward to serving you.
Sincerely,
Matt Zollman
Director of Operations & Product Management
- Published in Announcements
Poster Presentation: Detection of the Substituted Cathinone, Alpha-PiHP, in Postmortem Toxicology Cases
By Kevin Shanks, D-ABFT-FT
In October, I traveled to the Society of Forensic Toxicologists (SOFT) annual meeting in Denver, CO and was able to present information about the newly emerged substituted cathinone, alpha-PiHP, and its detection in postmortem toxicology cases in Florida. Any applicable details of these postmortem cases were provided by the following offices and we thank them for their contributions to this presentation.
1. District 2 Medical Examiner’s Office, Tallahassee, Florida; Dr. Lisa Flanagan and Dr. Jon Throgmartin
2. District 14 Medical Examiner’s Office, Panama City, Florida; Dr. Jay Radtke
3. District 15 Medical Examiner’s Office, West Palm Beach, Florida; Dr. Catherine Miller and Dr. Heidi Reinhard
We have previously discussed alpha-PiHP on this blog but I’d like to summarize the poster presentation here.
Substituted cathinones, derivatives of the naturally occurring cathinone, are a class of novel psychoactive substances (NPS) that have emerged across the world since the early 2000s and have been implicated in morbidity and mortality.
Alpha-PiHP is a substituted cathinone that is an isomer of the prescription medication pyrovalerone, which is a norepinephrine-dopamine reuptake inhibiting drug that is used as an appetite suppressant and for the treatment of chronic fatigue. Alpha-PiHP was first reported as being a drug sold in Slovenia in 2016 and in the USA in 2018. This compound acts similarly to other classical stimulants such as methamphetamine with pharmacological activity involving the neurotransmitters serotonin, norepinephrine, and dopamine. Reported effects after use of substances such as these include increased alertness, increased energy, euphoria, feelings of well-being, restlessness, and hallucination. Other physiological effects are hyperthermia, tachycardia, hypertension, mydriasis, diaphoresis, dehydration, and hyponatremia.
Due to reports of the recent increase of alpha-PiHP in the US, in December 2022, we added the substance to our scope of comprehensive testing in postmortem blood samples. Qualitative identification of alpha-PiHP was undertaken by a protein precipitation extraction with acetonitrile followed by liquid chromatography with quadrupole time of flight mass spectrometry (LC-QToF-MS) detection. The limit of detection for alpha-PiHP was 5 ng/mL.
For the first five months (01/01/2023 – 06/01/2023), we identified the presence of alpha-PiHP in seven different postmortem blood samples in Florida. It was detected as the sole substance in two cases and was detected alongside fentanyl in three cases and dimethylpentylone/pentylone in two cases. Details were not able to be acquired or published for all cases, but in the three cases where cause of death certification was available, alpha-PiHP was implicated in all three as the drug of toxicological interest.
As with any NPS, it is important that a toxicology laboratory assesses regional and temporal drug trends and prevalence for the locations which submit work to them and adapt their scopes of testing. If a laboratory is not screening for alpha-PiHP, it is possible to miss potentially positive casework.
Please reach out to us if you have any questions regarding this poster, substituted cathinones, alpha-PiHP, or interpretation of results for a case involving alpha-PiHP. We can be reached at 317-759-4869 option 3 or [email protected]. A copy of the poster is available as a PDF file upon request. If you’d like to collaborate on a future presentation or publication, please do not hesitate to reach out to us. We’d love to work with you!
- Published in Drug Classes, General
Poster Presentation: Examination of Several Cases of Mitragynine Toxicity Resulting in Death From 2020-2023
By Stuart Kurtz, D-ABFT-FT,
This past October, I travelled to the annual meeting for the National Association of Medical Examiners (NAME) with our CEO, Phil Roberts, in San José, CA. While there, we had the pleasure of meeting with several of you and discussing how to best serve you and your offices going forward. We always look forward to these conversations both at conferences like NAME and throughout the year as your needs change.
This year I presented a poster that looked at 5 cases of mitragynine overdoses. Details of these cases were provided by the following offices and we thank them for their contributions.
Examination of Several Cases of Mitragynine Toxicity Resulting in Death From 2020-2023
- Office of the District Medical Examiner, District 15 FL, Dr. Wendolyn Sneed
- Office of the Coroner, Lorain County, OH, Dr. Frank P. Miller
- Forensic Medicine and Pathology, Big Horn County, WY, Dr. Thomas L. Bennett
- Office of the Coroner Stark County, OH, Dr. Ronald R. Rusnak
- St. Luke’s Hospital, IA, Dr. Ned Austin
Mitragynine is the primary alkaloid in the kratom plant. While not federally scheduled, some states have restrictions in place on the sale of kratom. At low doses, mitragynine acts as a “cocaine-like” stimulant while at higher doses users report “opioid-like” effects. An important thing to remember is that while mitragynine has activity at the mu opioid receptor, it does NOT affect the β-arrestin pathway. This is responsible for respiratory depression associated with compounds such as fentanyl, morphine, and the nitazenes.
There is no clinical data available for mitragynine so therapeutic, toxic, and fatal ranges are unknown. DUID case reports have found a range of 11-490 ng/mL. Internally, our cases have a median concentration of 76.4 ng/mL. Case circumstances and scene investigation are important in the interpretation of mitragynine levels. Low concentrations of mitragynine in blood are typically not of concern but we are happy to assist in the interpretation of the results.
Mitragynine is often not included in routine toxicology testing and most emergency departments, due to the nature of their testing procedures, will also not test for it. Comprehensive panels such as Axis’ Comprehensive Panel with Analyte Assurance™ will typically include testing for it. Because of the loose regulations regarding the sale of kratom, labelled bags of plant material or bottles of capsules can be identified at the scene. This can be vital in guiding testing recommendations if it’s suspected that it could be involved.
Please reach out to us if you have any questions regarding this poster, kratom in general, or interpretation of results for a case involving mitragynine. We can be reached at 317-759-4869 option 3 or [email protected]. We can email a copy of the poster upon request
- Published in Drug Classes, General
A Closer Look at the Novel Emerging Compounds Panel: AP-237 and Brorphine
By Kevin Shanks, M.S., D-ABFT-FT
As mentioned in previous blog posts, novel psychoactive substances (NPS) come in different varieties and the Novel Emerging Compounds (NEC) Panel offered by Axis Forensic Toxicology helps to detect the most newly emerged NPS on the drug market and is meant to evolve over time as new drugs emerge on the street. In this series, we have taken a look at the recently emerged substances bromazolam, flubromazepam, alpha-PiHP, N,N-dimethylpentylone, phenibut, and tianeptine. In this fourth and final post in the series, we will take a brief look at two more recently emerged opioids: AP-237 and brorphine.
AP-237, also known as 1-butyryl-4-cinnamylpiperazine or Bucinnazine, is an opioid analgesic substance that is used as a prescription medication in China to treat pain. AP-237 is considered to be equipotent to morphine as an analgesic. AP-237 and a methylated derivative, 2-methyl-AP-237, recently emerged on the illicit drug market in the United States. AP-237 is currently unscheduled in the United States and not considered a controlled substance.
Brorphine is an opioid substance that was originally synthesized in 2018 by researchers who were investigating various opioids with the intention of finding safer analgesics that produce less respiratory depression than the typical prescription opioids used as medications. Brorphine was first detected on the illicit drug market in the United States in 2019 – 2020, but now has also been found in Europe. It is currently controlled as a Schedule I controlled substance in the United States.
Both of these substances function as opioid receptor agonists in the human body. Similar to other opioids, such as morphine and fentanyl, they bind to opioid receptors in the central nervous system (brain and spinal cord) and produce an analgesic effect. In overdose, they may cause severe central nervous system depression to include respiratory depression. When the breathing slows down, apnea can occur. Apnea leads to hypoxia – or lack of oxygen distribution to the surrounding tissues including the brain. Hypoxia can lead to cardiac arrest and death.
Axis qualitatively monitors both of these compounds in our NEC panel (order code 13710) and Comprehensive Panel, Blood with Analyte Assurance (order code 70510) using liquid chromatography with quadrupole time of flight mass spectrometry (LC-QToF-MS). Over the time range 01/30/2023 – 06/30/2023, Axis did not detect AP-237, but did detect brorphine in 1 blood specimen in Indiana. In Axis Forensic Toxicology casework, brorphine was detected alongside diphenhydramine, clonazolam, acetylfentanyl, fentanyl, morphine, 6-acetylmorphine, butonitazene, isotonitazene, metodesnitazene, metonitazene, and protonitazene.
As you can see from the prevalence data, both AP-237 and brorphine are rarely detected in blood by the toxicology laboratory, but it is still vital that we monitor them for the immediate future as NPS are a geographical and temporal phenomenon.
Axis also monitors other NPS in the following available panels of testing.
- The Novel Psychoactive Substances panel (order code 13610) include 25B-NBOMe, 25C-NBOMe, 25I-NBOMe, 2C-B, 2C-E, 2C-I, 5-MeO-DALT, adinazolam, alpha-PVP, butylone, clonazolam, dibutylone, dimethylone, ethylone, etizolam, eutylone, flualprazolam, flubromazolam, MDPV, mephedrone, methcathinone, methedrone, methoxetamine, methylone, N-ethylpentylone, pentylone, and TFMPP.
- The Designer Opioids panel (order code 13810) includes 4-ANPP, acetylfentanyl, acrylfentanyl, betahydroxythiofentanyl, butyrylfentanyl, carfentanil, cis-3-methylfentanyl, cyclopropylfentanyl, furanylfentanyl, isobutyrylfentanyl, methoxyacetylfentanyl, ocfentanil, parafluorobutyrylfentanyl, parafluoroisobutyrylfentanyl, tetrahydrofuranfentanyl, and U-47700.
- The Nitazenes Analog panel (order code 13910) includes butonitazene, etodesnitazene, etonitazene, flunitazene, isotodesnitazene, isotonitazene, metodesnitazene, metonitazene, N-pyrrolidinoetonitazene, and protonitazene.
As always, if you have questions about these substances and how they may play a role in your medical-legal investigation, please reach out to our subject matter experts by email ([email protected]) or phone (317-759-4869, Option 3).
- Published in Drug Classes