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.

A Fatality Related to the Synthetic Opioid U-47700: Postmortem Concentration Distribution.

In this case report, we present an evaluation of the distribution of postmortem concentrations of 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) in a fatality attributed principally to the drug. A man who had a history of drug abuse was found unresponsive and not breathing on his bed. Drug paraphernalia, indicating drug insufflation, was located in the decedent's room. Toxicology screening tests in peripheral blood initially identified U-47700 using an alkaline drug screen with gas chromatography-mass spectrometry (GC-MS) following solid-phase extraction. It was subsequently confirmed and quantitated by GC-MS-specific ion monitoring analysis following liquid-liquid extraction. The U-47700 peripheral blood concentration was quantitated at 190 ng/mL compared to the central blood concentration of 340 ng/mL. The liver concentration was 1,700 ng/g, the vitreous was 170 ng/mL, the urine was 360 ng/mL and the gastric contained only a trace amount (<1 mg). Other drugs detected in peripheral blood were alprazolam (0.12 mg/L), nordiazepam (<0.05 mg/L), doxylamine (0.30 mg/L), diphenhydramine (0.14 mg/L), ibuprofen (2.4 mg/L), salicylic acid (<20 mg/L) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (2.4 ng/mL). The cause of death was certified as acute U-47700 and alprazolam abuse, and the manner of death was certified as accident.

Gabapentin concentrations and postmortem distribution.

Gabapentin is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. Gabapentin has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional self-poisonings, serious effects are generally rare. In this report, gabapentin analyses were performed on 30 postmortem cases that had peripheral blood, central blood and liver tissue. Overall the central to peripheral blood (C/P) ratio mean was 0.90±0.24 (mean±standard deviation), and a median of 0.97. The liver to peripheral blood (L/P) ratio mean was 0.68±0.26L/kg (mean±standard deviation), and a median of 0.65L/kg. An additional case, where both antemortem blood and postmortem peripheral blood specimens were available, revealed the same gabapentin concentration in both specimens. Taken together, the data presented suggests that gabapentin is unlikely to show postmortem redistribution.

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.

An acute gabapentin fatality: a case report with postmortem concentrations.

Gabapentin (GBP) (Neurontin®, Horizant®, Gralise®) is a widely prescribed medication used primarily for the treatment of epilepsy and neuropathic pain. GBP has a favorable adverse effect profile in therapeutic dosing with the most common reported effects being dizziness, fatigue, drowsiness, weight gain, and peripheral edema. Even with intentional GBP self-poisonings, serious effects are rare. A 47-year-old female was found dead at work with her daughter's bottle of GBP 600 mg. There were 26 tablets missing and the decedent's only known medication was hydrocodone/acetaminophen. Following initial detection by an alkaline drug screen (GC-MS), analysis utilizing specific liquid chromatography-mass spectrometry revealed an elevated postmortem GBP peripheral blood concentration of 37 mg/L, central blood 32 mg/L, liver 26 mg/kg, vitreous 32 mg/L, and gastric contents 6 mg. Screening for volatiles, drugs of abuse, alkaline compounds, and acid/neutral compounds was negative with the exception of ibuprofen (<2 mg/L) detected in peripheral blood. This report presents a fatality that appears to be associated with an isolated and acute GBP ingestion.

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).

Acute 3,4-methylenedioxy-N-ethylcathinone (ethylone) intoxication and related fatality: a case report with postmortem concentrations.

A 30-year-old man reportedly ingested pills and used illicit drugs with another person. They both fell asleep that night and the following afternoon the other person found him dead. There were used hypodermic needles and a metal spoon with dark tarry substance at the death scene, and two recent puncture sites were found on his body. It was uncertain if he had a history of illicit drug use. Postmortem blood initially screened borderline positive for methamphetamine by ELISA. An alkaline drug screen-detected ethylone which was subsequently confirmed and quantified by a specific GC-MS SIM analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.39 mg/L), central blood (0.38 mg/L), liver (1.4 mg/kg), vitreous (0.58 mg/L), urine (20 mg/L) and gastric contents (12 mg). Other compounds detected in peripheral blood were morphine (0.05 mg/L), alprazolam (<0.05 mg/L), delta-9-THC (<1 ng/mL), delta-9-carboxy-THC (3.6 ng/mL) and naproxen (<5 mg/L). A urine screen (GC-MS) also confirmed 6-monoacetylmorphine, codeine and sildenafil. The cause of death was certified due to mixed ethylone, heroin and alprazolam intoxication. The manner of death was certified as accident.

Fatal metformin intoxication with markedly elevated blood and liver concentrations.

The highest postmortem metformin concentrations are recorded utilizing a sensitive and specific analytical procedure. The peripheral blood metformin concentration was 240 mg/L, the liver concentration was 240 mg/kg and the gastric concentration was 1,700 mg. Additionally, an antemortem blood sample collected shortly after admission revealed a metformin concentration of 210 mg/L. These data, revealing a liver to peripheral blood ratio of 1.0, provide additional support that metformin is not subject to postmortem redistribution. Intentional self-poisonings with metformin can result in death, despite multiple medical interventions.

Two deaths attributed to the use of 2,4-dinitrophenol.

We report the cases of two individuals, one in Tacoma, WA, and the second in San Diego, CA, whose deaths were attributed to ingestion of 2,4-dinitrophenol (2,4-DNP). 2,4-DNP has historically been used as a herbicide and fungicide. By uncoupling mitochondrial oxidative phosphorylation, the drug causes a marked increase in fat metabolism that has led to its use to aid weight loss. Both cases reported here involved its use for this purpose. Features common to both cases included markedly elevated body temperature, rapid pulse and respiration, yellow coloring of the viscera at autopsy, history of use of weight loss or body building supplements, and presence of a yellow powder at the decedent's residence. Because of its acidic nature, the drug is not detected in the basic drug fraction of most analytical protocols, but it is recovered in the acid/neutral fraction of biological extracts and can be measured by high-performance liquid chromatography or gas chromatography-mass spectrometry. The concentration of 2,4-DNP in the admission blood samples of the two deaths reported here were 36.1 and 28 mg/L, respectively. Death in both cases was attributed to 2,4-DNP toxicity. Review of information available on the internet suggests that, although banned, 2,4-DNP is still illicitly promoted for weight loss.

The analysis of an intracerebral hematoma for drugs of abuse.

Toxicological investigations were performed on an intracerebral hematoma, antemortem blood, and postmortem blood of an individual who was found unresponsive in his home. The hematoma was found to have ethanol at a concentration of 0.05% (w/v), and benzoylecgonine (a cocaine metabolite) was also confirmed at a concentration of 0.43 mg/L by specific analysis using gas chromatography/mass spectrometry (GC/MS). These results enabled the pathologist to record the cause of death as intracerebral hemorrhage due to acute cocaine intoxication.