3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive, synthetic analog of the central nervous system stimulant cathinone. Its recent popularity as a recreational drug in the United States has led to numerous reports to poison control centers across the country. As with other synthetic cathinones, the recreational use of MDPV has resulted in death. MDPV is thought to exert its pharmacologic effects by inhibiting the reuptake of dopamine and norepinephrine. This report describes the case of an exposure of a 39-year-old male to MDPV, which resulted in his death. Postmortem concentrations of MDPV in various tissues were measured. The detection of MDPV in tissues and fluids was accomplished using gas chromatography-mass spectrometry analysis after solid-phase extraction. Blood analysis also demonstrated therapeutic levels of lamotrigine, fluoxetine, risperidone, benztropine, pseudoephedrine and ibuprofen. The detection of cathinones in hair was conducted using high-performance liquid chromatography-tandem mass spectrometry after solid-phase extraction. MDPV was uniformly distributed among multiple tissues (blood, brain, muscle, cerebrospinal fluid and lung) at concentrations of approximately 0.4 to 0.6 µg/mL. Tissue and fluids responsible for detoxification/excretion had higher concentrations of MDPV (kidney, liver and bile > 0.8 µg/mL). A blood concentration ≥ 0.4 µg/mL was judged sufficient to cause death. The cause of death was ruled MDPV intoxication resulting in cardiac arrhythmia.

In July of 2016, carfentanil (CF) emerged in Northeast Ohio resulting in over 25 deaths within a 30-day period. A total of 125 deaths have occurred in Summit County and Cuyahoga County has reported 40 deaths, relating to the presence of CF either alone, or in combinations with heroin and fentanyl. Prior to this surge in CF cases, positive fentanyl enzyme-linked immunosorbent assay (ELISA) screening results were increasing in number. Many were negative for fentanyl confirmation by gas chromatography-mass spectrometry. Fentanyl analogs such as CF, acetyl fentanyl (AF), 2-furanyl fentanyl (2-Fu-F) and 3-methylfentanyl (3-MF) may be present in these cases. Some fentanyl analogs like CF and 3-MF do not cross-react with the Immunalysis ELISA fentanyl assay. With the emergence of potent synthetic fentanyl analogs, questions arose as to how to interpret their very low concentrations or absence in the blood in relation to cause of death. Driving under the influence of drugs (DUID) blood specimens had also tested positive for CF by reference laboratories. A liquid chromatography-tandem mass spectrometry method was developed to identify and quantify fentanyl, norfentanyl (NF) and four analogs: AF, 2-Fu-F, 3-MF and CF. The method has been utilized to quantify these fentanyl analogs in blood and vitreous humor in authentic antemortem and postmortem cases. Calibration curves were established between 0.10-4.0 ng/mL (NF, AF, 3-MF, 2-Fu-F and CF) and 1.0-40 ng/mL for fentanyl. In total, 98 postmortem cases analyzed produced the following blood concentration ranges: CF (0.11-0.88 ng/mL), 3-MF (0.15-1.7 ng/mL), 2-Fu-F (0.15-0.30 ng/mL), AF (0.14-0.16 ng/mL), fentanyl (1.1-15 ng/mL) and NF (0.10-3.7 ng/mL). Only CF, fentanyl and NF were detected in a statistically significant subset DUID population of 26 cases producing concentration ranges between 0.11 and 0.47 ng/mL, 1.0 and 9.8 ng/mL, and 0.11 and 3.5 ng/mL, respectively.

Postmortem toenail samples were used for the detection of cocaine (COC), benzoylecgonine (BZE), norcocaine (NCOC), cocaethylene (CE), morphine (MOR), 6-monoacetylmorphine (6-MAM), codeine (COD), and hydrocodone (HDC). After the toenail clippings were washed with methanol, they were solubilized in 0.1 M potassium phosphate (pH 5.0). The drugs of interest, along with internal standards, were isolated by solid-phase extraction followed by derivatization with N-methyl-N-trimethylsilyl-trifluoroacetamide. The derivatized products were analyzed by gas chromatography-mass spectrometry operated in the selective ion monitoring (SIM) mode. The limit of quantitation for all analytes was 0.3 ng on column. The quantities of drugs found in toenails of each of 46 decedents were compared with those of their corresponding postmortem fluids. The toenails of the 46 decedents were tested for COC, BZE, NCOC, and CE, and 34 of the collected samples were also tested for opiates. COC and BZE concentrations ranged from 0.20 to 140.17 (n = 20) and 0.30 to 315.44 ng/mg (n = 21), respectively. NCOC concentrations of 6.78 and 0.66 ng/mg and CE concentrations of 2.60 and 0.73 ng/mg were detected in two of the decedents' toenails. MOR and 6-MAM were detected in three sets of toenails at average concentrations of 0.37 and 0.89 ng/mg, respectively. COD was detected in two sets of specimens at concentrations of 3.07 and 1.02 ng/mg. HDC (0.62 ng/mg) was found in only one set of specimens.

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