Acute Intoxications Involving Valerylfentanyl Identified at the New York City Office of Chief Medical Examiner

Abstract

The detection of novel fentanyl analogs in both seized drugs and toxicological specimens has presented a significant challenge to laboratories with respect to identification, sourcing reference drug standards, time required for method development and ensuring sufficient method sensitivity. The New York City Office of Chief Medical Examiner (NYC OCME) has included testing for valerylfentanyl as part of a panel of synthetic opioids since May 2017 but did not identify the first valerylfentanyl positive case until July 2018. Unlike many other illicit fentanyl analogs that were briefly identified before being replaced with a new analog, valerylfentanyl has persisted over time and continues to be identified in New York City acute polydrug intoxications. Since July 2018, a total of 69 cases were identified with valerylfentanyl present, but there were no cases where it was the sole intoxicant. 84% of decedents were male, with the majority between the ages of 50 and 59 years (39%) and were predominantly Hispanic (49%). The cause of death in all 69 cases involved acute polydrug intoxication, while the manner of death was deemed an accident in 68 cases and undetermined in one case. Concentrations of valerylfentanyl in postmortem blood ranged from < 0.10 to 21 ng/mL with 44.9% (N = 31) of the concentrations at or below the lower limit of quantification (0.10 ng/mL) but above the limit of detection (0.05 ng/mL). Fentanyl was present in 100% of the cases and in higher concentrations (1.6–116 ng/mL). The most common drug classes detected with valerylfentanyl were other opiates (76.8%), cocaine/metabolites (50.7%), benzodiazepines (29%), and ethanol (21.7%). Valerylfentanyl is a relatively unknown fentanyl analog with limited information in the scientific literature. This study presents the first publication detailing a series of postmortem cases involving valerylfentanyl in acute intoxications and includes key demographic information and femoral blood concentrations for improved interpretation and analysis.

Review of analytical methods for screening and quantification of fentanyl analogs and novel synthetic opioids in biological specimens

“…Extraction procedures utilized for LC–MS/MS quantitative methods are more expansive due to the applicability to multiple matrix types. While LLE [21,38,39,40,41,42,43,44,45] and SPE [23,37,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70] remain the most common techniques, PP [17,71,72,73,74,75,76,77,78,79,80,81,82], simple dilution [11,14,37,83] solvent extraction [82,84,85], SLE [86,87] and QuECHeERs [16,71,88] have been described as suitable extraction techniques among their evaluated scenarios. In some studies, sample pretreatment techniques such as PP and physical preparations (grinding [89,90], pulverization [62], and digestion [37]) were employed before extraction.…”

The rise and rise of fentanyl in postmortem casework

“…Comparing the first 6 months of 2022, acetylfentanyl and fluorofentanyl were identified in 124 and 554 postmortem cases, respectively. In the vast majority of cases where fentanyl analogs are present, fentanyl is also detected and there are few cases where a fentanyl analog is present alone, either as the only drug or only opioid present [7,8].…”

“…By March 2021, the method had been further expanded to 44 synthetic opioids plus xylazine. The detailed method parameters, including the list of synthetic opioids, were previously published [7,8] with limits of detection (LOD) of 0.05 and 0.10 ng/mL for fentanyl and fentanyl analogs.…”

The metabolism of valerylfentanyl using human liver microsomes and zebrafish larvae

“…In the 1980s, researchers recognized the need for reference materials to confirm the identity of fentanyl analogs and to evaluate their potency, therefore synthesizing many of which are re‐emerging today 4,5 . Valerylfentanyl was included as one of these compounds, and since then, it has been detected in wastewater effluents, postmortem samples, or seized drugs in North America, Australia, Europe, and Asia 6–11 . Figure 1 shows the structure of valerylfentanyl, a homolog of fentanyl, differing by 28 Da.…”

“…4,5 Valerylfentanyl was included as one of these compounds, and since then, it has been detected in wastewater effluents, postmortem samples, or seized drugs in North America, Australia, Europe, and Asia. [6][7][8][9][10][11] Figure 1 shows the structure of valerylfentanyl, a homolog of fentanyl, differing by 28 Da. A study of valerylfentanyl in monkeys showed that it was equipotent to morphine.…”