n-(1-phenethylpiperidin-4-yl)-n-phenylacetamide and Substance-Related-Disorders

In 2013, the Centers for Disease Control and Prevention released a warning regarding a new recreational drug, acetyl fentanyl. Acetyl fentanyl is a μ-opioid receptor agonist, and its pharmacological effects include euphoria, altered mood, miosis and central nervous system depression. The objective of this report was to develop a sensitive and specific method for the quantitation of acetyl fentanyl by gas chromatography-mass spectrometry in postmortem casework. Acetyl fentanyl was isolated from biological matrices using solid-phase extraction and acetyl fentanyl-13C6 was employed as an internal standard. The method was validated utilizing the Scientific Working Group for Forensic Toxicology's published method validation parameters, and the biological matrices used for analysis were postmortem blood and urine. In addition to the quantitation of acetyl fentanyl, a demographic study of cases obtained from the Rhode Island Office of State Medical Examiners and the University of Florida Health Pathology Laboratories-Forensic Toxicology Laboratory was performed to examine potential risk factors for acetyl fentanyl use. The results from this study found that the blood concentrations in these individuals ranged from 17 to 945 ng/mL. This suggests acetyl fentanyl is less potent than its prototype drug, fentanyl and requires an increased dose to achieve its desired effects. The demographic analysis indicated white males aged 21-40 years and individuals with a previous history of drug use have the highest risk for acetyl fentanyl abuse.

Topics: Adult; Fentanyl; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Limit of Detection; Male; Postmortem Changes; Reproducibility of Results; Solid Phase Extraction; Substance Abuse Detection; Substance-Related Disorders; Young Adult

Recently, fentanyl analogs account for significant number of opioid deaths in the United States. Routine forensic analyses are often unable to detect and differentiate these analogs due to low concentrations and presence of structural isomers. A data-independent screening method for 14 fentanyl analogs in whole blood and oral fluid was developed and validated using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Data were acquired using Time of Flight (TOF) and All Ions Fragmentation (AIF) modes. The limits of detection (LOD) in blood were 0.1-1.0 ng/mL and 0.1-1.0 ng/mL in TOF and AIF modes, respectively. In oral fluid, the LODs were 0.25 ng/mL and 0.25-2.5 ng/mL in TOF and AIF modes, respectively. Matrix effects in blood were acceptable for most analytes (1-14.4%), while the nor-metabolites exhibited ion suppression >25%. Matrix effects in oral fluid were -11.7 to 13.3%. Stability was assessed after 24 h in the autosampler (4 °C) and refrigerator (4 °C). Processed blood and oral fluid samples were considered stable with -14.6 to 4.6% and -10.1 to 2.3% bias, respectively. For refrigerated stability, bias was -23.3 to 8.2% (blood) and -20.1 to 20.0% (oral fluid). Remifentanil exhibited >20% loss in both matrices. For proof of applicability, postmortem blood (n = 30) and oral fluid samples (n = 20) were analyzed. As a result, six fentanyl analogs were detected in the blood samples with furanyl fentanyl and 4-ANPP being the most prevalent. No fentanyl analogs were detected in the oral fluid samples. This study presents a validated screening technique for fentanyl analogs in whole blood and oral fluid using LC-QTOF-MS with low limits of detection.

Topics: Alfentanil; Chromatography, Liquid; Fentanyl; Forensic Toxicology; Furans; Humans; Illicit Drugs; Limit of Detection; Mass Spectrometry; Remifentanil; Saliva; Solid Phase Extraction; Substance Abuse Detection; Substance-Related Disorders; Sufentanil

Opioid analgesics are widely used in health care, yet have significant potential for abuse. High doses are associated with potentially fatal respiratory depression, which caused 21,314 deaths in the United States in 2011. Acetylfentanyl, a synthetic opioid agonist closely related to fentanyl, recently emerged as a drug of abuse linked to numerous deaths in North America.. A 36-year-old male developed the habit of using a propylene glycol electronic cigarette filled with acetylfentanyl to aid relaxation. He purchased the drug online in a manner that appeared legal to him, which compromised his insight about the danger of the substance. He had been using the e-cigarette with increasing frequency while on medical leave, and his wife reported finding him weakly responsive on more than one occasion. At approximately 3 am, the family activated 911 for altered mental status. His presentation included respiratory depression, pinpoint pupils, hypoxemia, and a Glasgow Coma Scale score of 6. He responded to serial doses of intravenous naloxone with improvement in his mental status and respiratory condition. Due to the need for repeated dosing, he was placed on a naloxone infusion and recovered uneventfully in intensive care. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Complications from emerging drugs of abuse, like acetylfentanyl, frequently present first to emergency departments. Prompt recognition and treatment can help avoid morbidity and mortality. Acetylfentanyl can be managed effectively with naloxone, although higher than conventional dosing may be required to achieve therapeutic effect.

Topics: Adult; Analgesics, Opioid; Fentanyl; Humans; Male; Psychotropic Drugs; Respiratory Insufficiency; Substance-Related Disorders

A man in his 30's was found at home, not breathing. He was admitted to an emergency hospital and the doctor confirmed his death. He had a history of methamphetamine abuse spanning several years, and while fresh needle marks were visible on his arm, the only other autopsy findings indicated an acute death. A small plastic bag containing a pale brown white powder, and a small amount of liquid in a syringe were found at the scene. The police forensic laboratory detected acetyl fentanyl and 4-methoxy PV8 (4-methoxy PHPP) in both the powder and the liquid. Scan analysis by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) identified acetyl fentanyl and 4-methoxy PV8 in the urine sample. Both drugs were quantitated simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using the selected reaction monitoring method. The concentration of acetyl fentanyl in the femoral vein blood, urine, and gastric contents were 153, 240, and 880ng/mL respectively, and the concentration of 4-methoxy PV8 in the femoral vein blood, urine, and gastric contents were 389, 245, and 500ng/mL respectively. Cause of death was attributed to acute poisoning by "bath salts" containing acetyl fentanyl and 4-methoxy PV8. Evidence indicated that self-administered intravenous injection was the most likely scenario, and that the deceased had been a habitual user of the "bath salt" drug for some time. Drugs detected in the gastric contents could be explained by the gastric secretion of basic drugs, or drug-containing bile entering the gastric contents.

Topics: Adult; Alkaloids; Designer Drugs; Fentanyl; Gastrointestinal Contents; Humans; Injections, Intravenous; Male; Narcotics; Substance-Related Disorders