Detection of a novel compound after overdoses of aspirin and amoxapine.

The identification of a novel by-product in the tissue and fluid extracts of a victim of fatal overdoses of the tricyclic antidepressant amoxapine and aspirin is presented. Gas chromatography/mass spectrometry suggested that amoxapine was transacetylated by aspirin to form N-acetylated amoxapine. When standard N-acetylated amoxapine was prepared and subjected to the same analytical testing as extracted tissues and fluids, the metabolite was identified as N-acetylamoxapine. Quantitation of N-acetylamoxapine was obtained by gas chromatography. Concentrations of N-acetylamoxapine compared to those of amoxapine and salicylates in blood, liver, stomach, and small bowel are given.

Estimation of perimortal percent carboxy-heme in nonstandard postmortem specimens using analysis of carbon monoxide by GC/MS and iron by flame atomic absorption spectrophotometry.

In decomposed, formalin-fixed, embalmed, exhumed, and some fire-dried cases in which normal blood is unavailable, the usual methods for determination of carboxyhemoglobin saturation frequently fail. To address these specimens, a method utilizing both gas chromatography/mass spectrometric (GC/MS) determination of carbon monoxide (CO) and flame atomic absorption spectrophotometry (FAAS) determination of iron (Fe), in the same specimen, was developed. The method is reported here, along with its application to seven pertinent forsensic death investigations. The CO analytical methodology involves acid liberation of the gas from the specimen aliquot in a headspace vial. After heating and equilibrating, a sample of the headspace vapor is injected into the GC/MS system with a gastight syringe. Quantitation is achieved by standard addition comparison utilizing the ideal gas law equation. Iron is quantified by FAAS analysis of the same aliquot used for the CO determination, following nitric acid digestion. The concentration is determined by comparison to a standard curve. A formula for determining the minimum percent carboxy-heme saturation was derived by using the ratio of the amount of CO to the amount of Fe in the aliquot analyzed. Tissue types analyzed include spleen, liver, muscle, dried blood, and unspecified decomposed tissue.

Differentiation of side chain isomers of ring-substituted amphetamines using gas chromatography/infrared/mass spectrometry (GC/IR/MS).

Common analytical methods used for identifying samples obtained from clandestine laboratories were evaluated for their ability to differentiate between possible amphetamine isomers and homologs. A series of ring-substituted (4-methyl, 4-methoxy, and 3,4-methylenedioxy) amphetamine and N-methylphenethylamine isomers was analyzed using color tests, thin-layer chromatography, gas chromatography/mass spectrometry (GC/MS) and GC/infrared (GC/IR). The N-acetyl derivatives of the isomers were analyzed using GC/IR/MS. GC/IR/MS readily differentiated the 4-methylphenylalkylamine isomers. MS and IR spectra were also obtained for each pair of the 4-methoxyphenylalkylamine isomers and the 3,4-methylenedioxyphenylalkylamine isomers, but differentiation via GC/IR/MS was difficult. The N-acetyl derivatives of each pair of isomers could be readily differentiated using GC/IR/MS. Good library researchable spectra for N-acetylamphetamine could be obtained for IR identification with 10 ng (on-column) and MS identification with 2 ng. The spectrometrically independent IR and MS data obtained for the N-acetyl derivatives indicated that the combination of GC/IR/MS can add a significant level of confidence in the analysis of ring-substituted arylalkylamines.

Aspirin acetylates the tricyclic antidepressant amoxapine spontaneously to N-acetylamoxapine in vitro and in vivo.

1. N-Acetylamoxapine is formed nonenzymically in vitro, and in mice, from amoxapine, a tricyclic antidepressant, and aspirin. 2. Formation of acetylamoxapine from amoxapine and aspirin in vitro was maximal at pH 5.0 since this pH optimized reactant solubilities as well as decreasing aspirin hydrolysis. 3. Formation of aceylamoxapine from amoxapine and aspirin in mouse stomachs was rapid, and the pH study indicates that the intestinal pH would favour formation even more. 4. Acetylamoxapine administered to mice produced the same CNS-related signs, leading to death, as with amoxapine, but much larger doses and longer time periods were required to elicit these effects. As brain and liver levels of amoxapine in animals dying from acetylamoxapine administration were less than half those found in animals given lethal doses of amoxapine, the toxicity in mice of acetylamoxapine may not be due solely to deacetylation of acetylamoxapine to the parent compound.

Occupational fatality and persistent neurological sequelae after mass exposure to hydrogen sulfide.

Exposure to hydrogen sulfide (H2S) has been associated with death as well as survival following coma with or without hypoxic brain damage. The release of H2S at a beachfront construction site led to the emergency evaluation and treatment of 37 people, with six admissions and one death. At least one victim, who underwent extensive therapy with hyperbaric oxygen, developed persistent neurological sequelae. Despite increased awareness of the potentially life-threatening consequences of exposure to H2S, significant poisoning continues to occur, even in workplaces where the hazards are well-known and can be avoided. Recommended therapy includes nitrites, hyperbaric oxygen, and supportive care, but documentation of efficacy is lacking. Because patients with chronic neurological sequelae after acute H2S exposure continue to be reported, we suggest that any survivor of H2S poisoning who presents in coma or who manifests objectively verifiable evidence of neurotoxicity on physical examination or lab testing should undergo baseline and annual neurological and neuropsychological testing for at least five years. This approach could standardize and enhance our knowledge of, and ability to detect, the subtle but permanent alterations of central nervous system function that follow H2S exposure.