By George S. Behonick, Ph.D., F-ABFT, Laboratory Director, Chief Toxicologist
Synthetic compounds designed to mimic the pharmacology of various illegal drug classes infiltrated the illicit drug market during the last decade plus; this includes synthetic cannabinoids (“K2 Spice”), cathinones (“Bath Salts”), hallucinogens, and designer fentanyl analogs and opioids (examples such as fluorofentanyl, brophine and the nitazene compounds). In particular, the fentanyl analogs, along with illicitly manufactured fentanyl (IMF), imposed significant impact to the morbidity and mortality of drug-related exposures. Heroin cases experienced a dramatic resurgence around 2010; in large part, its unprecedented purity (users could ‘snort’ or insufflate the drug) and its relative low cost compared to prescription opioids (e.g. OxyContin®) fueled its unbridled demand as an alternative among opioid addicts and neophyte users. Gradually with time, solid dose materials (paraphernalia) and autopsy specimens began to demonstrate the concomitant presence of heroin and IMF. Ostensibly, the addition of IMF was designed to increase the potency of the product. Eventually, beginning in 2014 the proportion of IMF became greater than heroin in these mixtures. By 2015 the greater number of drug-involved cases included fentanyl, and not heroin. Simultaneous to this trend, numerous synthetic fentanyl analogs were being manufactured outside of the United States, but made available to illicit drug traffickers over the Internet. In 2016-17, carfentanil began appearing in seized solid dose drug products and medical examiner death investigation cases .
Carfentanil is a mu (µ) opioid receptor agonist; it is about 10,000 times more potent than morphine and demonstrates 30-100 times the potency of fentanyl . Between September 1, 2016 and January 1, 2017, Axis Forensic Toxicology detected carfentanil in 262 postmortem blood specimens . We described the specific details of 13 fatalities, from Indiana, Michigan, Kentucky and Ohio in this data set. Other investigators reported the detection of carfentanil in blood specimens obtained from impaired drivers and postmortem toxicology submissions [7, 4]. In response, state and federal agencies issued health alerts in 2018 which detailed the rising numbers of deaths involving fentanyl and fentanyl analogs to include carfentanil [2, 1].
2016 and 2017 demonstrated a surge increase in the number of drug-related deaths in the United Sates; that is, ↑11,228 (+21.4%) in 2016 and ↑6605 (+10.4%) in 2017; however, notably in 2018, drug-related deaths declined by 2,870 or -4.1%. The rise and fall coincided with increases, and then, decreases of carfentanil detections in seizure exhibits from 2015-2018. The overall availability of carfentanil was attributed to be a major factor in the accelerated, then diminished rate of drug-related deaths in the period 2016-2018 . China banned carfentanil on March 1, 2017.
In CY 2022 Axis Forensic Toxicology detected carfentanil in two cases. Carfentanil was detected in one case in February 2023 however, in late spring and summer (May 26 – Aug 18), Axis Forensic Toxicology detected carfentanil in blood specimens from 9 postmortem cases. The time span being four months with the cases originating from four different states: Indiana (4), Wisconsin (2), Kentucky (2), and Ohio (1). A cursory review of a subset of these cases (n = 7) indicated 6 of 7 decedents to be male, with an age range of 29-61 years and median age of 41 years. Carfentanil postmortem blood concentrations exhibited a range of 47.2 to 409 picograms per milliliter (pg/mL); carfentanil was identified qualitatively in two of the cases. Multiple drugs were detected in all but one case. Fentanyl was detected in all cases with multiple drug detections. Methamphetamine and amphetamine was detected in 5 of the 7 cases. Other detections included: Acetylfentanyl (4 cases), 4-ANPP (4 cases), fluorofentanyl ( 1case) and morphine (1 case).
The aforementioned case accounts underscore the continued awareness and vigilance medico-legal death investigators and forensic toxicology laboratories must demonstrate to surveilling the drug carfentanil. In one case reported herein, the decedent, a 61 year old male, was found deceased in his vehicle at a truck stop that he was known to frequent on a near daily basis. The sole toxicological finding in this case was a carfentanil postmortem blood concentration of 403 pg/mL. In the two Wisconsin cases, the deaths occurred in two males who apparently knew each other and were suspected to have secured drugs from the same supplier within a close approximate time to each other. And in one Indiana case, investigators believed there was an association or a link to two other cases with respect to the source of the carfentanil. All three deaths occurred proximate to each other in time with a belief that the carfentanil supplier was one of the decedents. Detecting carfentanil in blood is a challenge because of the low (sub nanogram/mL or picogram/mL) presenting concentrations of the drug. Axis Forensic Toxicology presumptively screens for carfentanil in the Comprehensive panel (order code 70510) and the Indiana State Department of Health panel (test code 70575); this is accomplished by high resolution mass spectrometry ( Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry) via the Analyte Assurance™ feature of the Comprehensive panel. Confirmation and quantitation of carfentanil is accomplished by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in the Designer Opioids panel (order code 13810) with a carfentanil Lower Limit of Quantitation (LLOQ) of 10 pg/mL , or 0.010 ng/mL. Of note, carfentanil is not presumptively screened in the Drugs of Abuse panel (order code 70530), or in the customized Drugs of Abuse panel (Kentucky, order code 70555).
In summary, carfentanil exhibited a significant nationwide prevalence in postmortem cases in 2016-17; subsequent scheduling of the drug in the United States and a ban in China in 2017 resulted, in part, to a precipitous decline in positive postmortem cases. Axis Forensic Toxicology recognized a re-emergence of carfentanil in postmortem case work notably beginning the latter part of May 2023 and extending into August 2023 with a total of 9 detections from four states (IN, WI, KY and OH). Medico-legal death investigators, medical examiners, coroners and law enforcement agencies are urged to be alert to this observation. Death scene investigation, decedent social/drug history, autopsy and an appropriate scope of toxicology testing are of paramount importance in suspected drug-related cases. Drug intelligence trends in a given jurisdiction or region, as provided by local sources such as the Drug Enforcement Agency (DEA), law enforcement drug task forces together with information from state and federal drug testing laboratories are essential tools in identifying real time drug patterns in a specific location. Thus far in 2023, with the exception of 1 case from the total of 10, all of the carfentanil detections noted in the laboratory were punctuated by the parallel detections of IMF; likewise, methamphetamine and amphetamine was detected in 5 of the 7 cases reviewed as a subset to the ten case total observed thus far in 2023. Axis Forensic Toxicology will continue to monitor carfentanil case trends in the remainder of 2023.
The following individuals and jurisdictions are recognized for their contributions to this article by the provision of case investigative details, circumstances and decedent histories: Amy Lay, Medicolegal Death Investigator/Pathology Assistant, Lake County Coroner’s Office, IN; Steve Lockyear, Vanderburgh County, IN Coroner; Joe Hudson, Grayson County, KY Coroner; Josh Garvey, Iowa County, WI Deputy Coroner, and Dr. Robert F. Corliss, Professor and Autopsy Director-Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison.
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