norfentanyl and Substance-Related-Disorders

Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5-50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.

Topics: Adolescent; Adult; Aged; Alfentanil; Analgesics, Opioid; Benzamides; Child; Child, Preschool; Chromatography, Liquid; Female; Fentanyl; France; Furans; Humans; Infant; Infant, Newborn; Limit of Detection; Male; Middle Aged; Neonatal Abstinence Syndrome; Piperidines; Remifentanil; Retrospective Studies; Substance Abuse Detection; Substance-Related Disorders; Sufentanil; Tandem Mass Spectrometry; 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

We recently encountered a subject who died from an uncommon misuse of a fentanyl transdermal patch, chewing, followed by complications of aspiration of the patch. We report this case to alert medical examiners to the troubling trend of increased fentanyl patch abuse and its expanding range of misuses and associated morbidities. The decedent was a 28-year-old white male with a past medical history of prescription drug abuse who was pronounced dead in the emergency department shortly after arrival. An autopsy was completed and a tough but stretchy beige foreign body was identified lodged in a mainstem bronchus. Toxicological analysis of femoral blood showed methamphetamine, fentanyl and norfentanyl concentrations of 1456, 8.6 and 1.4 ng/mL, respectively. Individuals who abuse prescription medications often modify the route of administration of the drug from the intended method. As this case demonstrates, this choice can be fatal. The novel findings include a chewed patch, aspiration of a drug patch, and combination with an illicit drug at potentially lethal blood levels for both methamphetamine and fentanyl in a novice user.

Topics: Administration, Oral; Adult; Bronchi; Fentanyl; Forensic Pathology; Forensic Toxicology; Humans; Male; Mastication; Methamphetamine; Narcotics; Respiratory Aspiration; Substance-Related Disorders

Fatalities associated with fentanyl hydrochloride are increasingly seen in Massachusetts. Between September 2005 and November 2006, 5009 medicolegal investigations associated 107 deaths with licit or illicit fentanyl use, along with a co-detection of an opiate/opioid or cocaine/benzoylecognine, or both. Deaths associated with illicit fentanyl use occur in younger people (39.4 vs. 61.5 years) with higher fentanyl (17.1 ng/mL vs. 4.4 ng/mL) and lower morphine (76.9 ng/mL vs. 284.2 ng/mL) postmortem blood concentrations, and more frequent cocaine co-intoxication (65% vs. 3%), than deaths associated with illicit fentanyl use. A wide range of postmortem blood concentrations of fentanyl was detected (trace-280 ng/mL), with a minimum concentration of 7 ng/mL of fentanyl strongly associated with illicit use of fentanyl in poly-drug cases. The most commonly detected opiates/opioids in illicit fentanyl users were: morphine (29%), oxycodone (14.5%), and methadone (14.5%). Ethanol, cannabinoids, diazepam, citalopram, and diphenhydramine were each detected in greater than 10% of the licit fentanyl cases. Most fentanyl abusers died at their own home and their deaths were most often classified as accidental. Mapping of primary residences of decedents revealed conspicuous clustering of the illicit fentanyl use cases, as opposed to the random pattern in licit use cases. Fentanyl misuse is a public health problem in Massachusetts.

Topics: Accidents; Adult; Aged; Aged, 80 and over; Cannabinoids; Cause of Death; Central Nervous System Depressants; Cocaine; Dopamine Uptake Inhibitors; Drug Overdose; Ethanol; Female; Fentanyl; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Narcotics; Selective Serotonin Reuptake Inhibitors; Substance-Related Disorders