Since 2013, the Miami-Dade County Medical Examiner Department has experienced an increase in the number of opioid-related deaths. The majority of cases coincided with the introduction of fentanyl into the local heroin supply. From 2014 to 2015, Miami-Dade County experienced a near 600% increase in fentanyl-related deaths, followed by an additional 200% increase in 2016. In 2015, two novel fentanyl analogs were identified in medical examiner cases: beta-hydroxythiofentanyl and acetyl fentanyl. In 2016, four additional fentanyl analogs emerged: para-fluoroisobutyryl fentanyl, butyryl fentanyl, furanyl fentanyl and carfentanil, as well as the synthetic opioid U-47700. In order to address this epidemic, a method was developed and validated to identify 44 opioid-related and analgesic compounds in postmortem samples using ultra high performance liquid chromatography ion trap mass spectrometry with MSn capabilities. The limit of detection for all compounds ranged from 0.1 to 5 ng/mL, with a majority having MS3 spectral fragmentation. Blood, urine, liver or brain specimens from ~500 postmortem cases were submitted for analysis based on case history and/or initial screening results. Of those cases, 375 were positive for illicit fentanyl and/or one or more fentanyl analogs. Due to the potency of these compounds, they were almost always included in the cause of death. Worth emphasizing and extremely alarming is the detection of carfentanil in 134 cases, 104 of which were initially missed by gas chromatography mass spectrometry. By incorporating this sensitive, highly specific, and evolving screening procedure into the workflow, the toxicology laboratory continues to effectively assist the medical examiners in determining the cause and manner of death of decedents in Miami-Dade County.
Recently, clandestine drug lab operators have attempted to bypass controlled substances laws and regulations with "designer" compounds chemically and pharmacologically similar to controlled substances. For example, "bath salts" have erupted onto the scene as "legal highs" containing cathinone analogs that have produced severe side effects in users worldwide. These products have sparked concern among law enforcement agencies, and emergency bans have been placed on the sale of such items. Despite the increasing number of designer drugs available, there are few comprehensive screening techniques for their detection and quantification in biological specimens. The liquid chromatography triple quadrupole tandem mass spectrometry (LC-QQQ-MS/MS) method presented here encompasses over thirty important compounds within the phenethylamine, tryptamine, and piperazine designer drug classes. Analytes were determined by LC-QQQ-MS/MS in the multiple-reaction monitoring mode after mixed-mode solid-phase extraction. The bioanalytical method was fully validated according to recommended international guidelines. The assay was selective for all analytes with acceptable accuracy and precision. Limits of quantification were in the range of 1-10 ng/mL for each compound with limits of detection near 10 pg/mL. In order to evaluate its applicability in a forensic toxicological setting, the validated method was used to analyze post-mortem specimens from two cases that were suspected of containing designer drugs. The method was able to identify and quantify seven of these compounds at concentrations as low as 11 ng/mL. The method should have wide applicability for rapid screening of important new drugs of abuse at high sensitivity in both post- and ante-mortem forensic analysis.
In February 2003, the Miami-Dade County Medical Examiner Department reported the first known death in the country related to alpha-methyltryptamine (AMT). AMT is an indole analogue of amphetamine investigated in the 1960s as an antidepressant, stimulant, and monoamine oxidase inhibitor. Today, AMT is recognized as a powerful psychedelic drug among high school and college-aged men and women. Its popularity is partly due to the multitude of anecdotal websites discussing AMT as well as its legality and availability for purchase via the Internet prior to April 2003. Emergency designation of AMT as a Schedule 1 controlled substance by the Drug Enforcement Administration occurred shortly after the death in Miami-Dade County. The case in Miami involved a young college student who, prior to death, advised his roommate that he was "taking hallucinating drugs" and as a result had "discovered the secret of the universe". Approximately 12 h later, the roommate discovered the deceased lying in bed unresponsive. An empty 1-g vial of AMT was recovered from the scene and sent to the toxicology laboratory. Initial screening of urine by enzyme-multiplied immunoassay technique was positive for amphetamines, and the basic drug blood screen detected a small peak later identified by mass spectrometry as AMT. For quantitation, AMT was isolated using solid-phase extraction, derivatized with pentafluoropropionic anhydride, and analyzed using gas chromatography-mass spectrometry. Quantitative analysis was based upon m/z 276, 303, and 466 for AMT and m/z 306, 333, and 496 for the internal standard, 5-methoxy-alpha-methyltryptamine. A linear calibration curve from 50 to 500 ng/mL was used to calculate the concentration of AMT in the samples and controls. Blood, tissue, and gastric specimens were diluted to bring the observed concentration within the limits of the standard curve. Matrix matched controls were extracted and analyzed with each run. Postmortem iliac vein blood revealed 2.0 mg/L, gastric contents (48 g collected at autopsy) contained 9.6 mg total of AMT, liver contained 24.7 mg/kg, and the brain contained 7.8 mg/kg. An additional Medical Examiner case from another jurisdiction revealed 1.5 mg/L in antemortem serum.
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