Tizanidine distribution in a postmortem case.

The case of a 57-year-old white female who was found deceased at home by her husband is presented. A suicide note was found at the scene. No remarkable findings were observed at autopsy. Comprehensive toxicological analysis of the heart blood identified ethanol (0.16 g/dL), diazepam (1.1 mg/L), and tizanidine (2.3 mg/L). Blood concentrations of tizanidine following therapeutic use do not exceed 0.025 mg/L. The medical examiner ruled that the cause of death was combined ethanol and multiple drug intoxication, and the manner of death was suicide.

A fatality involving metaxalone.

A case is presented of a 54-year-old white female found dead in a secured apartment. Postmortem toxicologic analysis of the heart blood identified acetaminophen (97 mg/L), citalopram (0.4 mg/L), gabapentin (24 mg/L) and metaxalone (21 mg/L). The metaxalone concentration is within the range of previously reported fatalities involving metaxalone. The medical examiner ruled that the cause of death was metaxalone and gabapentin intoxication and the manner of death was suicide.

A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation.

A case of a 25-year-old white male who was found dead the morning after consuming herbal extracts containing beta-carbolines and hallucinogenic tryptamines is presented. No anatomic cause of death was found at autopsy. Toxicologic analysis of the heart blood identified N,N-dimethyltryptamine (0.02 mg/L), 5-methoxy-N,N-dimethyltryptamine (1.88 mg/L), tetrahydroharmine (0.38 mg/L), harmaline (0.07 mg/L), and harmine (0.17 mg/L). All substances were extracted by a single-step n-butyl chloride extraction following alkalinization with borate buffer. Detection and quantitation was performed using liquid chromatography-electrospray mass spectrometry. The medical examiner ruled that the cause of death was hallucinogenic amine intoxication, and the manner of death was undetermined.

Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose.

We report a case involving a fatal intoxication with loperamide (Imodium). Loperamide is a synthetic opioid of the phenyl piperidine class used as an over-the-counter antidiarrheal. It exerts its effects through interaction with micro-opiate receptors in the intestine to reduce peristalsis. Loperamide lacks the typical euphoric opiate effects when administered at recommended doses. Both loperamide and its major metabolite, N-desmethylloperamide, were isolated by liquid-liquid extraction into n-butyl chloride from alkalinized samples. Extracts were analyzed by liquid chromatography-electrospray-mass spectrometry in selected-ion-monitoring mode. Rapid separation of the drug, metabolite, and internal standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8-microm particle diameter. The mobile phase consisted of 0.1% formic acid in deionized water (60%) and acetonitrile (40%) at a flow rate of 0.5 mL/min. Heart blood concentrations for loperamide and its metabolite were 1.2 mg/L and 3.3 mg/L, respectively. In contrast, reported peak plasma concentrations of loperamide after administration of recommended daily doses of 16 mg did not exceed 0.012 mg/L in controlled trials. Because the heart blood ethanol concentration was 0.08 g/dL, the medical examiner ruled that the cause of death was loperamide and ethanol intoxication, and the manner of death as undetermined.

Mixed drug intoxication involving zaleplon ("Sonata").

Zaleplon ("Sonata") is a pyrazolopyrimidine derivative approved for use in the United States for the treatment of insomnia. To date, there has been little data in the toxicological literature where zaleplon has been implicated as causing a fatal intoxication, either alone or in combination with other drugs. This report documents a case where zaleplon was identified in a suicide by multiple drug ingestion. The following zaleplon concentrations were found: heart blood 2.2mg/l; bile 8.6mg/l and urine 1.4mg/l. Zaleplon was also detected but not quantitated in the kidney and liver.

Tentative identification of novel oxycodone metabolites in human urine.

Oxycodone is a semisynthetic codeine derivative that has been used both as an analgesic and antitussive. In the mid 1990s, OxyContin was introduced as a slow-release formulation of oxycodone for use in patients with moderate to severe chronic pain from such ailments as arthritis, vertebral disc disease, and cancer. Doctors wrote 6.9 million prescriptions for OxyContin from May 2000 through May 2001. Thus, it is no surprise that hospitals and medical examiners' offices across the country have seen an increasing number of admissions and deaths resulting from oxycodone abuse and overdose. The laboratory identifies oxycodone as part of its routine abused and therapeutic drug-testing procedures. Routine gas chromatographic analysis of bile or urine in many of these cases revealed unidentified peaks in the region of oxycodone that appeared to be oxycodone metabolites. In humans, the only documented metabolites of oxycodone are oxymorphone and N-desmethyloxycodone (noroxycodone). This study attempts to characterize these compounds as "presumptive" metabolites based on circumstantial evidence from known metabolic pathways of oxycodone in other species, as well as of other opiates and narcotic analgesics.

Hydroxycarbazepine distribution in three postmortem cases.

This paper presents three cases investigated by the Office of the Chief Medical Examiner where hydroxycarbazepine, the active metabolite of the anticonvulsant prodrug oxcarbazepine, was detected in the biological specimens submitted for toxicological analysis. Hydroxycarbazepine was quantitated using a single-step pH 5 extraction and detection on a DB-5 column by gas chromatography-nitrogen-phosphorus detection. In the three cases, the heart blood concentrations were 34.6, 40.5, and 3.7 mg/L, respectively. In cases 2 and 3, the peripheral blood concentrations were 36 and 4.1 mg/L, respectively. In each case, the medical examiner ruled that the hydroxycarbazepine was an incidental finding to the cause of death.

Analysis of metformin in antemortem serum and postmortem specimens by a novel HPLC method and application to an intoxication case.

A case of intoxication from the oral hypoglycemic drug metformin is presented. A number of published liquid chromatographic methods were combined to enable a simplified analysis of metformin in both antemortem and postmortem specimens. The method involved direct injection of a protein-free filtrate into the liquid chromatograph. The method was sufficiently sensitive to detect therapeutic use of metformin; no common therapeutic or abused drugs interfered with the assay. In the presented case, the hospital admission serum metformin concentration was 141 mg/L, or approximately two orders of magnitude above therapeutic concentrations. The medical examiner concluded that the cause of death in this case was metformin intoxication, and the manner of death was suicide.

Distribution of triazolam and alpha-hydroxytriazolam in a fatal intoxication case.

The case of a 77-year-old woman who was found dead in her bathtub with her head clearly above the water line is presented. The decedent had a medical history of depression, liver disease, spinal stenosis, and diabetes mellitus. An empty medication bottle of triazolam was found in the trashcan. At autopsy, no injury or evidence of drowning was found. Toxicological analysis identified triazolam at a concentration of 0.12 mg/L in the heart blood. Triazolam and alpha-hydroxytriazolam were quantitated in the specimens received. The medical examiner ruled that the cause of death was triazolam intoxication and the manner of death was suicide.

Tissue distribution of xylazine in a suicide by hanging.

Xylazine (Rompun, Sedazine, AnaSed) is currently the most commonly used sedative-analgesic in veterinary medicine. There are nine published cases of xylazine's involvement in human drug-related deaths and impairment. However, blood concentrations were reported in only four of these cases. Three of these nine cases were fatalities involving xylazine, two of which involved xylazine alone but did not report blood concentrations because of extensive decomposition of the bodies. This report documents a case in which xylazine alone was identified in a suicide by hanging. The following xylazine concentrations were found: 2.3 mg/L in heart blood; 2.9 mg/L in peripheral (subclavian) blood; 6.3 mg/L in bile; 0.01 mg/L in urine; 6.1 mg/kg in liver; and 7.8 mg/kg in kidney.

Oxycodone intoxication in an infant: accidental or intentional exposure?

A case is presented of a 10 month old male who went into cardiac arrest at a local store. The infant subsequently expired and was autopsied at the Office of the Chief Medical Examiner, State of Maryland. The only remarkable finding was the detection of oxycodone in the postmortem specimens; the blood and liver oxycodone concentrations were 0.6 mg/L and 1.6 mg/kg, respectively. Oxycodone was identified and quantitated by gas chromatography-nitrogen-phosphorus detection and confirmed by full scan electron ionization gas chromatography-mass spectrometry. The medical examiner ruled that the cause of death was oxycodone intoxication, and the manner of death was homicide. The key toxicologic question in this case was whether or not it was reasonable for the infant to be exposed to oxycodone exclusively through breast milk or through an alternate source. It was concluded that, at best, there were serious concerns about the likelihood of drug exposure through consumption of breast milk.

A comparison of carboxyhemoglobin saturation values in postmortem heart blood and peripheral blood specimens.

The following is a study conducted to determine whether there was any significant difference in carboxyhemoglobin (COHb) saturation levels between the heart blood and blood collected from a peripheral site. The average heart blood to peripheral blood COHb saturation level ratio in the 42 cases studied was 1.09. Sixty-two percent (26 of 42) of the cases had a heart blood to peripheral blood ratio between 0.9 and 1.1; 74% (31 of 42) had a ratio between 0.8 and 1.2. Eighty-three percent (35 of 42) had a ratio between 0.7 and 1.3. There were four cases where the heart blood to peripheral blood ratio was either below 0.6 or greater than 1.4. The differences between the two sites were not statistically significant.

Fatal diphenhydramine intoxication in infants.

Diphenhydramine is an antihistamine available in numerous over-the-counter preparations. Often used for its sedative effects in adults, it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death. Reports of fatal intoxications in young children are rare. We present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child's father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities. We review the literature on diphenhydramine toxicity, particularly as it pertains to small children, and discuss the rationale for treating these cases as fatal intoxications.