Iain M. McIntyre

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.

Postmortem tissue concentrations of venlafaxine

Venlafaxine is a phenethylamine antidepressant which inhibits both serotonin and norepinephrine reuptake and is structurally unrelated to the serotonin reuptake inhibitors (SSRIs). Its major metabolite, O-desmethylvenlafaxine (ODV), also inhibits serotonin reuptake. Although metabolized by the cytochrome P-450 (CYP) system, venlafaxine inhibits CYP 2D6 and 3A4 to a far lesser extent than do the SSRIs. Mechanisms of drug action are reviewed and evaluated in the investigation of 12 fatalities occurring over a 6-month-period where venlafaxine was detected.Venlafaxine and ODV were identified by liquid chromatography-mass spectrometry (LC-MS) using atmospheric pressure ionization (API) electrospray in positive mode following an n-butyl chloride extraction. Postmortem tissue concentrations studied in each of 12 postmortem cases for venlafaxine and ODV, were 0.1-36 and <0.05-3.5mg/l (peripheral blood), <0.05-22 and <0.05-9.9mg/kg (liver), <0.05-10 and <0.05-1.5mg/l (vitreous), <0.05-53 and <0.05-6.8mg/l (bile), <0.05-55 and <0.05-21mg/l (urine), respectively, and 0.1-200mg of venlafaxine in the gastric contents. Venlafaxine was typically present with other drugs, including other antidepressants, alcohol, and benzodiazepines. The potential for interaction with each drug is discussed. Over the 6-month-period of this study, there were no deaths ascribed solely to venlafaxine intoxication.

Postmortem Carisoprodol and Meprobamate Concentrations in Blood and Liver: Lack of Significant Redistribution

Carisoprodol is a therapeutic and occasionally abused centrally acting muscle relaxant. We compare central blood and liver concentrations of carisoprodol and the metabolite meprobamate to concentrations in peripheral blood in 11 medical examiner cases. Specimens were initially screened for alcohol and simple volatiles by gas chromatography (GC)-flame ionization detection headspace analysis, enzyme-linked immunosorbent array for drugs of abuse, and therapeutic drugs by GC-mass spectrometry (MS). Carisoprodol, when detected by the therapeutic drug screen, was confirmed and quantified by a specific GC-MS procedure. The results suggest that when ingested with other medications, carisoprodol may be a contributing factor in death, even when present at therapeutic concentrations. Considering the cases studied, together with previously published therapeutic and fatal concentrations, blood carisoprodol concentrations greater than 15 mg/L and liver concentrations greater than 50 mg/kg may be considered excessive and potentially fatal. Carisoprodol central blood to peripheral blood ratios averaged 1.31 + 0.33 (mean ± standard deviation), and liver to peripheral blood, 2.83 ± 1.51. Meprobamate central blood to peripheral blood ratios averaged 0.92 ± 0.22, and liver to peripheral blood, 1.25 ± 0.69. The low liver to peripheral blood ratio (less than 5), taken together with the low central blood to peripheral blood ratio, is an indicator that both carisoprodol and meprobamate lack the potential to exhibit postmortem redistribution.

EXTRACTION OF PSYCHOTROPIC DRUGS FROM HUMAN SCALP HAIR

A comparison of techniques for the extraction of antidepressant and antipsychotic drugs in human scalp hair is described. Human scalp hair was obtained from cadavers known to be taking psychotropic drugs prior to their death. Following a washing step, hair was either solubilized in sodium hydroxide, or treated with dilute hydrochloric acid, methanol or subtilisin. Digests were treated with a solvent and the extracted drugs quantified by high performance liquid chromatography. The alkaline digestion procedure was found to be significantly more effective (P < 0.01) in recovering a range of antidepressant and antipsychotic drugs from hair than either the acidic, methanolic or enzymatic treatments.

A Fatality Involving Moclobemide, Sertraline, and Pimozide

A case is described involving a suspected fatal interaction between moclobemide and sertraline, in combination with the use of pimozide.

Detection of antidepressant and antipsychotic drugs in postmortem human scalp hair.

The presence of therapeutic drugs in postmortem human scalp hair was investigated. Hair samples from 21 cadavers known to have taken antidepressant and antipsychotic drugs were solubilized in 1 M sodium hydroxide. Drugs were extracted using solvent extraction procedures and analyzed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). Antidepressant drugs detected were amitriptyline, dothiepin, doxepin, imipramine, trimipramine, and mianserin. Antipsychotic drugs detected were haloperidol, chlorpromazine and thioridazine. Concentrations of these drugs and their metabolites ranged from 1.3 to 242 ng/mg hair. Segmental analysis demonstrated that the drug concentrations detected were either consistent with the known dosing regime of the deceased, or were able to provide an indication of drug use within the last few months prior to death. This study reinforces the potential of hair as a useful tissue in forensic investigations, in establishing a history of past exposures to therapeutic drugs.

A Study Involving Venlafaxine Overdoses: Comparison of Fatal and Therapeutic Concentrations in Postmortem Specimens

The distribution and redistribution of venlafaxine were investigated in two overdoses and several cases involving the therapeutic use of venlafaxine. Blood, liver, bile vitreous humor, urine and gastric contents were analyzed using high performance liquid chromatography with ultraviolet detection. Blood concentrations of venlafaxine in the two overdose cases were 53 mg/L and 78 mg/L. Comparison of venlafaxine concentrations in blood samples taken at different times after death revealed increases in concentrations over time, suggesting the possible postmortem redistribution of venlafaxine.

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.

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 decedents 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 monitoringxa0analysis 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.

Acute methylone intoxication in an accidental drowning - A case report

A 19-year-old woman who was known to use illicit drugs (ecstasy and marijuana) was found floating in the ocean 100 yards from the beach. When last seen the previous evening, she had said to a friend that she was going to get in the water. Reports to police indicated that she may have been on ecstasy. There were no notes of a suicidal nature, illicit drugs, drug paraphernalia, tobacco cigarettes, or alcoholic beverages at the scene. Autopsy findings were consistent with drowning. Postmortem blood initially screened positive for methamphetamine and cannabinoids by ELISA and was subsequently confirmed for methylone by a specific GC-MS SIM analysis following solid-phase extraction. Concentrations found in the peripheral blood, central blood, vitreous, liver and gastric contents were measured at 3.4 mg/L 3.4 mg/L, 4.3mg/L, 11 mg/kg, and 1.7 mg, respectively. No other amphetamine-like compound (including ecstasy) was detected. These results are discussed in relation to previous cases of toxicity, and the lack of potential for substantial methylone postmortem redistribution.