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.
Ketamine, an anesthetic agent primarily used in veterinary medicine and pediatrics, continues to gain in popularity in the drug abuse scene or 'Rave Wave' of all-night dance clubs. The Division of Forensic Toxicology Laboratory (Office of the Armed Forces Medical Examiner) at the Armed Forces Institute of Pathology, as the primary analytical laboratory for criminal investigative agencies in the Department of Defense (DOD), has seen requests for ketamine analysis rise from 1 in 1997 to 116 in 2000. This increasing abuse has led the DOD Urine Drug Testing Laboratories to consider adding ketamine screening to their random urinalysis program. However, before ketamine testing can be implemented as standard policy, concentrations of ketamine and metabolites in urine need to be evaluated after actual drug use. There is very little information regarding the pharmacokinetics of ketamine, especially concentrations of the drug or its two major metabolites, norketamine and dehydronorketamine, that can be expected in urine. In fact, dehydronorketamine has been believed to be an analytical artifact caused by the high temperatures of gas chromatography. In this paper, we attempt to resolve this issue with the development of a liquid chromatography-mass spectrometry (LC-MS) method. The urine concentrations of ketamine, norketamine and dehydronorketamine (presumptive) detected in 33 "positive" cases received in our laboratory since 1998 are reported. Quantitations were accomplished with LC-MS. Ketamine concentrations ranged from 6 to 7744 ng/mL. Norketamine concentrations ranged from 7 to 7986 ng/mL and dehydronorketamine (presumptive) concentrations ranged from 37 to 23,239 ng/mL.
Pharmacokinetic studies of psilocybin in humans have shown the rapid dephosphorylation of psilocybin to psilocin with further conversion to 4-hydroxy-tryptophole (4HT) and 4-hydroxyindole-3-acetic acid (4HIAA) in plasma. Our study shows that psilocin also undergoes conjugation and can be found in the urine as the psilocin-glucuronide conjugate. Recoveries after enzymatic hydrolysis of the urine with β-glucuronidase (Helix Pomatia or E. Coli) when compared to non-hydrolyzed urine confirmed the presence of the glucuronide. Detection of psilocin from hydrolyzed and extracted samples was optimized for GC/MS by derivatization with MSTFA. The method developed allows for the detection of psilocin in urine with a limit of quantitation of 10 ng/mL, based on 5 mL of spiked urine. Using this method, our laboratory has confirmed the presence of psilocin in 6 out of 8 urine samples, with concentrations ranging from 10 ng/mL to greater than 200 ng/mL. Before implementation of the hydrolysis and derivatization steps, our limit of detection was 200 ng/mL, based on spiked urine standards. No case samples were positive without hydrolysis and derivatization.
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.
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