An evaluation of postmortem concentrations of Δ9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH).

Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, leads to impaired cognitive and psychomotor function resulting in an increased risk of fatal motor vehicle collisions and other traumas resulting in death. It is important to measure cannabinoids in postmortem cases to improve understanding of this growing public safety issue. However, postmortem concentrations of THC and its primary inactive metabolite, 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH), have not been extensively studied. We aim to further characterize postmortem concentrations of THC and THCCOOH in peripheral blood with and without preservation, central blood, and central "serum" to support improved forensic interpretation. Cannabinoids were extracted from blood and "serum" from twenty-five decedents using solid phase extraction followed by quantification using gas chromatography - mass spectrometry. We evaluated the impact of sample preservation, reported central blood-to-peripheral blood (CB:PB) ratios and blood-to-"serum" ratios, and assessed the relationship of CB:PB and postmortem interval for THC and THCCOOH. Correlations of preserved compared to unpreserved blood were strong with r2 > 0.97. The median CB:PB ratios were 1.1 and 1.3 for THC and THCCOOH, respectively. THCCOOH CB:PB was significantly higher than 1.0 (p-value < 0.001). The CB:PB ratio was only weakly correlated with PMI for both compounds. The median blood-to-"serum" ratio was 1.0 for THC and 0.8 for THCCOOH. The blood-to-"serum" ratio of THCCOOH was significantly lower than 1.0 (p-value < 0.001). Results demonstrated minimal potential for postmortem redistribution of THC and THCCOOH and that the ratio of blood-to-"serum" in postmortem samples differs from the blood-to-plasma ratio established in living humans. Based on these results, it is not recommended to apply a correction factor to THC and THCCOOH concentrations from postmortem blood samples. Our study improves the understanding of postmortem cannabinoid concentrations to support forensic interpretation in cases of fatal motor vehicle accidents.

An Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations.

In this case report, we present an evaluation of the distribution of postmortem concentrations of butyr-fentanyl in a fatality attributed principally to the drug. A man who had a history of intravenous drug abuse was found unresponsive on the bathroom floor of his home. Drug paraphernalia was located on the bathroom counter. Toxicology testing, which initially screened positive for fentanyl by enzyme-linked immunosorbent assay, subsequently confirmed butyr-fentanyl, which was then quantitated by gas chromatography-mass spectrometry-specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. The butyr-fentanyl peripheral blood concentration was quantitated at 58 ng/mL compared with the central blood concentration of 97 ng/mL. The liver concentration was 320 ng/g, the vitreous was 40 ng/mL, the urine was 670 ng/mL and the gastric contained 170 mg. Acetyl-fentanyl was also detected in all biological specimens tested. Peripheral blood concentration was quantitated at 38 ng/mL compared with the central blood concentration of 32 ng/mL. The liver concentration was 110 ng/g, the vitreous was 38 ng/mL, the urine was 540 ng/mL and the gastric contained <70 mg. The only other drug detected was a relatively low concentration of benzoylecgonine. The cause of death was certified as acute butyr-fentanyl, acetyl-fentanyl and cocaine intoxication, and the manner of death was certified as accident.

A Fatality Related to Two Novel Hallucinogenic Compounds: 4-Methoxyphencyclidine and 4-Hydroxy-N-methyl-N-ethyltryptamine.

In this case report, we present an evaluation of postmortem concentration distribution of the hallucinogenic compound 4-methoxyphencyclidine (4-MeO-PCP) in a fatality principally attributed to this drug. Another hallucinogen, 4-hydroxy-N-methyl-N-ethyltryptamine was also detected, but was not quantitated. A man--who had a history of recent 'strange' behavior--was found deceased, on his bed, in his locked room. Toxicology testing, which initially screened positive for phencyclidine (PCP) by ELISA, subsequently detected and confirmed the two hallucinogens by gas chromatography-mass spectrometry. 4-MeO-PCP concentrations were then quantified by a specific secondary testing technique. The peripheral blood concentration was 8.2 mg/L compared with the central blood concentration of 14 mg/L. The liver concentration was 120 mg/kg, the vitreous was 5.1 mg/L, the urine was 140 mg/L and the gastric contents contained 280 mg. PCP was not detected, but therapeutic concentrations of venlafaxine, olanzapine, lorazepam and hydroxyzine were confirmed. The cause of death was certified due to acute mixed drug intoxication, and the manner of death was certified as accident.

An Acute Acetyl Fentanyl Fatality: A Case Report With Postmortem Concentrations.

In this case report, we present an evaluation of the distribution of postmortem concentrations of acetyl fentanyl in a fatality attributed to the drug. A young man who had a history of heroin abuse was found deceased at his parents' home. Toxicology testing, which initially screened positive for fentanyl by ELISA, subsequently confirmed acetyl fentanyl by gas chromatography-mass spectrometry specific ion monitoring (GC-MS SIM) analysis following liquid-liquid extraction. No other drugs or medications, including fentanyl, were detected. The acetyl fentanyl peripheral blood concentration was quantified at 260 ng/mL compared with the central blood concentration of 250 ng/mL. The liver concentration was 1,000 ng/kg, the vitreous was 240 ng/mL and the urine was 2,600 ng/mL. The cause of death was certified due to acute acetyl fentanyl intoxication, and the manner of death was certified as an accident.

Acute 5-(2-aminopropyl)benzofuran (5-APB) intoxication and fatality: a case report with postmortem concentrations.

A 20-year-old man, a college student, became unresponsive in front of his girlfriend. He was known to consume alcohol and take an unknown drug at some point while in attendance at a local music festival earlier in the day/evening. Upon arrival of emergency personnel, he was noted to be asystolic and apneic. Despite aggressive medical intervention by emergency personnel and at a local hospital emergency room, he was pronounced deceased within 1.25 h of initial medical attention. Postmortem blood initially screened positive for methamphetamine by ELISA. An alkaline drug screen detected 5-(2-aminopropyl)benzofuran (5-APB) which was subsequently confirmed and quantified by a specific GC-MS SIM analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (2.5 mg/L), central blood (2.9 mg/L), liver (16 mg/kg), vitreous (1.3 mg/L), urine (23 mg/L) and gastric contents (6 mg). No other common amphetamine-like compound was detected, although 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-APDB) was presumptively identified in both peripheral blood and urine. Alcohol, the only other drug identified, was confirmed at a concentration of 0.02% (w/v).

Mitragynine 'Kratom' related fatality: a case report with postmortem concentrations.

A 24-year-old man whose medical history was significant for alcohol abuse and depression was found unresponsive in bed. He had several prior suicide attempts with 'pills' and had also been hospitalized for an accidental overdose on a previous occasion. Autopsy findings were unremarkable apart from pulmonary edema and congestion, and urinary retention. Postmortem peripheral blood initially screened positive for mitragynine 'Kratom' (by routine alkaline drug screen by gas chromatography-mass spectrometry, GC-MS), which was subsequently confirmed by a specific GC-MS selective ion mode analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.23 mg/L), central blood (0.19 mg/L), liver (0.43 mg/kg), vitreous (<0.05 mg/L), urine (0.37 mg/L) and was not detected in the gastric. Therapeutic concentrations of venlafaxine, diphenhydramine and mirtazapine were also detected together with a negligible ethanol of 0.02% (w/v). The results are discussed in relation to previous cases of toxicity, and the lack of potential for mitragynine postmortem redistribution.

Hydroxyzine distribution in postmortem cases and potential for redistribution.

Hydroxyzine is an antihistaminic with sedative properties used in the control of anxiety and emesis. Peripheral blood hydroxyzine concentrations are compared to central blood and liver concentrations in 10 medical examiner cases. Specimens were initially screened for alcohol and simple volatiles by GC-FID headspace analysis, ELISA for drugs of abuse, and alkaline drugs by GC/MS. Hydroxyzine, when detected by the alkaline drug screen, was subsequently confirmed and quantified by a specific GC-NPD procedure. Data suggest that postmortem peripheral blood hydroxyzine concentrations may be considered therapeutic to at least 0.24 mg/L and corresponding liver concentrations to at least 4.9 mg/kg. Hydroxyzine concentrations ranged 0.07-3.0mg/L in peripheral blood, 0.04-3.8 mg/L in central blood, and 0.88-55 mg/kg in liver. Hydroxyzine central blood to peripheral blood ratios averaged 0.92±0.25 (±standard deviation; N=6). Liver to peripheral blood ratios, on the other hand, were higher and averaged 13.8±6.2 (±standard deviation; N=10). Given that a liver to peripheral blood ratio less than 5 is consistent with little to no postmortem redistribution while exceeding 20-30 is indicative of propensity for significant postmortem redistribution, these data suggest that hydroxyzine is prone to a moderate degree of postmortem redistribution.