Acute fatal poisoning with cyamemazine

A case of fatal poisoning with cyamemazine is presented. The cyamemazine was identified in post-mortem blood using a specific gas chromatographic/mass spectrometry method. The autopsy blood concentration of cyamemazine was 1800 ng/ml. Chronic use of cyamemazine was demonstrated by the presence of the drug in hair. Two other drugs were also detected (bromazepam and trimeprazine). We think that this current blood concentration (1800 ng/ml) is a fatal blood concentration because of the negativity of the other parameters, but careful interpretation of analytical findings are important, the possibility that this death was a consequence of the toxicity of combined drugs could not be excluded. Not many therapeutics and toxic levels were previously reported in overdosage cases in which cyamemazine was involved. We consider that this concentration is only of guidance value for a fatal cyamemazine poisoning.     

The trend in lethal poisonings with narcotic substances in Moscow

The analysis of the 1989-2005 records of the Moscow Bureau of Forensic-Medical Examinations, statistics on lethal narcotic poisonings by gender, age, education, social and family status has revealed that the trend to reduction of the number of narcotic substances (NS) poisonings stopped in 2003. There was a 238.4% rise in the above poisonings in 2004. The highest rise was in the age group of 21-25-year-olds (35.7%; CI = 0.34-0.37; p = 0.05) and 26-30-year-olds (29.6%; CI = 0.28-0.31; p = 0.05). Among lethal cases one-third were unemployed (35.8%; CI = 0.34-0.37; p = 0.05) and one-forth were workers (22.2%; CI = 0.20-0.24; p = 0.05). By the family status, most of the dead were unmarried (57%; CI = 0.55-0.59; p = 0.05). This study gives a complete and accurate picture of the structure of narcotic drug poisonings. Relevant preventive measures are proposed.     

Acute intoxication with orphenadrine and clozapine.

This report describes a fatal intoxication with two different drugs: clozapine and orphenadrine. A 38-year-old man was found dead in the bedroom of his residence. Near the body were found various empty pharmaceutical boxes, employed in schizophrenic therapy, two of them containing clozapine and orphenadrine. High concentrations of clozapine and orphenadrine detected in blood, urine and gastric content were related to death. These compounds were identified and quantitated by liquid-liquid extraction followed by gas chromatographic/mass spectrometry (GC/MS) analysis.     

HPLC-ESI-MS/MS determination of zuclopenthixol in a fatal intoxication during psychiatric therapy.

The first non-suicidal fatality due to intramuscular administration of Cisordinol (zuclopenthixol, ZPT) is described. A new, rapid, and sensitive method for the determination of ZPT in postmortem specimens has been developed. High performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was employed for drug confirmation and quantitation. Sample clean up was performed using a simple liquid-liquid extraction procedure. The postmortem concentration of ZPT in heart blood was 0.68 microg/ml. Furthermore, zotepine, carbamazepine, and chlorprotixene were detected in body fluids. The proposed method enables the unambiguous identification and quantitation of ZPT and other neuroleptic drugs in clinical and forensic specimens.     

A fatal forensic intoxication with fenarimol: analysis by HPLC/DAD/MSD

Fenarimol (Rubigan) is a pyrimidine ergosterol biosynthesis inhibitor used as a systemic fungicide. The authors present a fatal fenarimol intoxication case analysed in the Forensic Toxicology Service of the National Institute of Legal Medicine. The results were used to compare two different HPLC techniques, regarding selectivity and sensitivity: an HPLC system with a diode array detector (DAD) and an HPLC system with a DAD and a mass spectrometry detector (MSD) with an electrospray interface. All biological samples were submitted to a solid-phase extraction procedure. The detection and quantification limits of fenarimol, linearity, precision and accuracy were evaluated. The fenarimol concentration levels determined were of 89.0 mg/ml in gastric contents, 1.9 mg/g in liver and 0.4 mg/g in kidney. Blood was not available at autopsy. No published data related to fenarimol self-poisoning were found, so it was not possible to interpret the results obtained by comparison with toxic/lethal levels.     

Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine.

Mixed drug reactions are frequently encountered in emergency department overdose cases and also in fatal intoxications. Assessment of the relative contribution of each drug in producing adverse effects is often compounded by lack of case history and the paucity of cases reported in the literature. This report describes a fatal intoxication with three common over-the-counter medications: guaifenesin, diphenhydramine, and chlorpheniramine. A 48-year-old woman was found dead in the attic bedroom of her residence. Specimens obtained at autopsy for toxicologic analysis included heart blood, urine, bile, gastric contents, vitreous humor, and cerebrospinal fluid. The over-the-counter drugs were identified and quantitated by acid/neutral or basic liquid-liquid extraction followed by gas chromatographic analysis with nitrogen phosphorus detection. Concentrations of guaifenesin, diphenhydramine, and chlorpheniramine detected in the heart blood were 27.4, 8.8, and 0.2 mg/L, respectively. The cause of death was determined to be acute intoxication by the combined effects of guaifenesin, diphenhydramine, and chlorpheniramine, and the manner of death was determined to be suicide. To our knowledge, the blood guaifenesin concentration in this case is the highest reported concentration to date associated with an acute intoxication.     

Halogenated solvent interactions with N,N-dimethyltryptamine: formation of quaternary ammonium salts and their artificially induced rearrangements during analysis

The psychoactive properties of N,N-dimethyltryptamine (DMT) 1a are known to induce altered states of consciousness in humans. This particular attribute attracts great interest from a variety of scientific and also clandestine communities. Our recent research has confirmed that DMT reacts with dichloromethane (DCM), either as a result of work-up or storage to give a quaternary N-chloromethyl ammonium salt 2a. Furthermore, this was observed to undergo rearrangement during analysis using gas chromatography-mass spectrometry (GC-MS) with products including 3-(2-chloroethyl)indole 3 and 2-methyltetrahydro-beta-carboline 4 (2-Me-THBC). This study further investigates this so far unexplored area of solvent interactions by the exposure of DMT to other halogenated solvents including dibromomethane and 1,2-dichloroethane (DCE). The N-bromomethyl- and N-chloroethyl quaternary ammonium derivatives were subsequently characterised by ion trap GC-MS in electron and chemical ionisation tandem MS mode and by NMR spectroscopy. The DCE-derived derivative formed at least six rearrangement products in the total ion chromatogram. Identification of mass spectrometry generated by-products was verified by conventional or microwave-accelerated synthesis. The use of deuterated DCM and deuterated DMT 1b provided insights into the mechanism of the rearrangements. The presence of potentially characteristic marker molecules may allow the identification of solvents used during the manufacture of controlled substances, which is often neglected since these are considered inert.