Faculty Bibliography

Ketamine is a dissociative anesthetic used in veterinary and human medicine since the 1970s. Its clinical use has expanded to control of seizures, pre-hospital emergency medical services (EMS), and is finding new purpose as an analgesic alternative and antidepressant. Ketamine brings hope for effective management of chronic pain in the absence of opioids, and decreasing suicidal ideations, however, its persistence as a recreational drug for its hallucinogenic properties remains. In the wake of expanding medicinal purposes, the diversity of New York City's population was explored to better understand its misuse. This retrospective study looks at the prevalence of ketamine in driver fatalities over a period of 18 years (2003-2020) and cases involving suspected driving under the influence of drugs (DUID) over a period of 6 years (2015-2020). Ketamine was identified in 6 driver fatalities and in 47 DUID cases. None of the driver fatalities were suspected of ketamine misuse, due to administration either in hospital or EMS administration. In the DUID cases, an increasing trend was observed over the 6-year study period with 100% (N = 47) of the cases confirmed as non-hospital/non-EMS administered ketamine. Of the DUID cases, 94% were male, with the majority between the age of 21-39 years (85%) and were predominantly Hispanic (36%) and Asian (34%). Blood concentrations of ketamine ranged from 27 to > 2000 ng/mL with polydrug use prevalent. The most common drug classes detected in addition to ketamine were cannabinoids (38%), ethanol (32%), benzodiazepines (26%), cocaine (19%), and amphetamines/MDMA (15%). In 2019, 2-fluoro-deschloroketamine (2F-DCK) was identified in two cases for the first time. Despite its increased acceptance for mental health disorders, ketamine's persistence and misuse as a recreational drug remains and should continue to be monitored by relevant toxicological, clinical, and law enforcement communities along with emerging illicit ketamine analogs.

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.

BACKGROUND:Illicitly manufactured fentanyl and fentanyl analogues (IMFs) are being increasingly suspected in overdose deaths. However, few prior outbreaks have been reported thus far of patients with laboratory-confirmed IMF toxicity after reporting intent to use only nonopioid substances. Herein we report a case series of nine patients without opioid use disorder who presented to two urban emergency departments (EDs) with opioid toxicity after insufflating a substance they believed to be cocaine. CASE REPORTS/METHODS:Over a period of under three hours, nine patients from five discrete locations were brought to two affiliated urban academic EDs. All patients denied prior illicit opioid use. All patients endorsed insufflating cocaine shortly prior to ED presentation. Soon after exposure, all developed lightheadedness and/or respiratory depression. Seven patients received naloxone en route to the hospital; all had improvement in respiratory function by arrival to the ED. None of the patients required any additional naloxone administration in the ED. All nine patients were discharged home after observation. Blood +/- urine samples were obtained from eight patients. All patients who provided specimens tested positive for cocaine metabolites and had quantifiable IMF concentrations, as well as several detectable fentanyl derivatives, analogues, and synthetic opioid manufacturing intermediates. DISCUSSION/CONCLUSIONS:IMF-contamination of illicit drugs remains a public health concern that does not appear to be restricted to heroin. This confirmed outbreak demonstrates that providers should elevate their level of suspicion for concomitant unintentional IMF exposure even in cases of non-opioid drug intoxication. Responsive public health apparatuses must prepare for future IMF-contamination outbreaks.

Background: The opioid epidemic remains a significant public health problem in the United States. Illicitly manufactured fentanyl and fentanyl analogues (IMFs) are being increasingly identified in overdose deaths. Fentanyl is approximately 100 times more potent than morphine, and IMFs have become an economical way to adulterate or replace heroin among illicit drug distributors and patients with opioid use disorder (OUD). While adulteration by IMFs is increasingly recognized among patients with OUD, what has received less attention is the contamination of non-opioid illicit substances, such as cocaine, with IMFs. There are few prior outbreaks that have been reported thus far of patients with laboratory-confirmed IMF toxicity after reporting intent to use only nonopioid substances. Herein we report a case series of nine patients without OUD who presented to two urban emergency departments (EDs) with opioid toxicity after insufflating a substance they believed to be cocaine. Case Reports: Over a period of under three hours, nine patients from five discrete locations were brought to two affiliated urban academic EDs. All patients were in their third decade of life and denied prior illicit opioid use. Two patients reported prior opioid exposure in the form of prescribed analgesics only, both more than one year prior. One patient reported a remote history of deep venous thrombosis; all others denied any significant past medical history. All patients endorsed insufflating cocaine shortly prior to ED presentation. Over the seconds to minutes following insufflation, all patients developed lightheadedness, and seven patients lost consciousness. In all cases of loss of consciousness, Emergency Medical Services responded and found the patients to have varying degrees of respiratory depression. These seven patients received naloxone en route to the hospital (Table 1) and all had improvement in respiratory function by arrival to the ED. None of the patients required any additional naloxone administration in the ED. All nine patients reported nausea and/or emesis which resolved with symptomatic treatment. All nine patients were discharged to home after an observation period. Blood samples were obtained from eight patients, and urine samples from six of these. One patient declined laboratory testing. All patients who provided specimens tested positive for cocaine metabolites and had quantifiable IMF concentrations, as well as several detectable fentanyl derivatives, analogues, and synthetic opioid manufacturing intermediates. (Table 2) Discussion: The geographic and temporal proximity of our patients' presentations, combined with the overlap in fentanyl precursors and analogues found on laboratory testing strongly suggests a common source, though sample product was not available for confirmation. Interpretation of this data is subject to a number of limitations, including variations in time between exposure and lab collection limiting interpatient comparability.
Conclusion(s): IMF-contamination of illicit drugs remains a public health concern that does not appear to be restricted to heroin. Increasing prevalence implies that providers should elevate their level of suspicion for concomitant IMF exposure even in cases of non-opioid drug intoxication. Responsive public health apparatuses need to prepare for future IMF-contamination outbreaks. (Table Presented)

Over the past three decades, many studies employing hollow-fiber liquid-phase microextraction (HF-LPME) bioanalytical methods have been published. The basic mechanism of extraction relies on the migration of the analytes through a liquid membrane sustained in the pores of the walls of a porous hollow fiber, and from there into an acceptor phase present in the lumen of the fiber. The mass transfer occurs by passive diffusion and it can be enhanced by using a carrier or applying an electrical potential across the phases. This type of extraction method presents many advantages over classical techniques, such as high preconcentration factor, clean extracts, and a green chemistry approach. Due to its advantages, and considering that no study systematically compiled the characteristics of the published methods in one single accessible source of information, the aim of this systematic review is to assess the data regarding bioanalytical methods, compile, and analyse the studies published until up to October of 2017. The data source used for the systematic review were Pubmed, Web of Science, and Science Direct, and 171 studies were included in the final review by two independent reviewers, resulting in a reliable and accessible source of information about bioanalytical methods employing HF-LPME.

Fatty acid ethyl esters (FAEEs) and ethyl-glucuronide (EtG) in meconium have been widely studied as biomarkers of maternal alcohol consumption during pregnancy. Many analytical approaches have been proposed for their analysis, mostly consisting of separated extraction procedures requiring the use of two meconium aliquots. This study aimed to validate a new analytical procedure for the simultaneous extraction of FAEEs and EtG from a meconium aliquot through a single solid-phase extraction (SPE) applied to 242 anonymized samples of meconium. Targeted FAEEs were: ethyl-myristate (Myr), ethyl-palmitate (Pal), ethyl-oleate (Ole) and ethyl-stearate (Ste). Two hundred milligrams of meconium was sonicated with acetonitrile, and a single SPE performed by means of aminopropyl columns. FAEEs were eluted with hexane, followed by EtG elution with water. Both the mixtures were dried, recovered, and analyzed by liquid chromatography-tandem mass spectrometry using C8 (FAEEs) and C18 (EtG) columns. Transitions were: m/z 257 --> 57,88, Myr; m/z 262 --> 57,88, Myr-d5; m/z 285 --> 57, 72, Pal; m/z 290 --> 57,258, Pal-d5; m/z 311 --> 72,114, Ole; m/z 316 --> 72,265, Ole-d5; m/z 257 --> 57,72 Ste; m/z 318 --> 57,286, Ste-d5; m/z 221 --> 75,85, EtG; m/z 226 --> 75,85, EtG-d5. Lower limit of quantification range was 10-15 ng/g for FAEEs and 10 ng/g for EtG. Linearity was evaluated for different concentration ranges; the mean coefficients of determination (R 2) were above 0.9961. Precision and accuracy for FAEEs and EtG were consistently