Simultaneous determination of cardenolides by sonic spray ionization liquid chromatography-ion trap mass spectrometry--a fatal case of oleander poisoning.

Simultaneous determination of oleandrin and its three related compounds, desacetyloleandrin, oleandrigenin, and gitoxigenin in blood by using liquid chromatography-three-dimensional quadrupole mass spectrometry (LC-3DQMS) system equipped with sonic spray ionization (SSI) interface was conducted. This analyzing method was suitable for all of these compounds except gitoxigenin. The limits of detection of oleandrigenin and desacetyloleandrin from blood were 2 ng/mL and that of oleandrin was 3 ng/mL. The calibration curves for oleandrin, desacetyloleandrin, and oleandrigenin were linear in the range of 5-100 ng/mL. The coefficients of variation of oleandrin, desacetyloleandrin, and oleandrigenin in the blood were satisfactory ranging from 1.6% to 4.1%. This analysis method was applied to a fatal case of oleander poisoning. As a result of liquid chromatography-mass spectrometry (LC-MS) analysis, oleandrin was detected in heart blood and cerebrospinal fluid. Desacetyloleandrin, oleandrigenin, and gitoxigenin were not detected. In order to make identification of oleandrin reliable, LC-MS-MS analysis was performed. The concentrations of oleandrin found in the heart blood and cerebrospinal fluid were 9.8 and 10.1 ng/mL, respectively.

Quantitative analysis of cresol and its metabolites in biological materials and distribution in rats after oral administration.

We investigated kinetics of p-cresol, m-cresol, and their glucuronide and sulfate metabolites in blood and organs of rats. We established a quantitative analysis method for the measurement of the concentrations of cresols. Endogenous beta-glucuronidase, an enzyme which hydrolyses the glucuronide, existed in rat organs, and it influenced the procedures for cresol hydrolysis of sulfatase. It was necessary for the quantitative analysis of cresol sulfate in organs to add the saccharolactone (d-saccharic acid 1,4-lactone) as an inhibitor for beta-glucuronidase. On the other hand, endogenous sulfatase did not interfere in the quantitative analysis of the glucuronide. It was found that cresol administered via the stomach tube diffuses directly through gastric and small intestinal walls because the unconjugate cresol concentrations were extremely high not only in the liver, but also in the spleen. The unconjugates of cresol in the liver, spleen and kidney were detected in high concentrations even when the unconjugates were not detected in the blood. m-Cresol was easily metabolized to sulfate, and the p-cresol to glucuronide in rats. The concentration ratios of m-cresol to p-cresol in blood and organs were different from the rate of the cresol soap solution that was administered. The pharmacokinetics was different between p-cresol and m-cresol in rats.

A case of fatal trichlorfon and methidathion poisoning.

A 50-year-old man, suspected of ingesting organophosphorus insecticides, was found dead in a graveyard. In the gas chromatography-mass spectrometric screening, trichlorfon and methidathion were detected in his gastric contents. The quantitative analysis for trichlorfon and methidathion was carried out by high-performance liquid chromatography. The concentrations (microg/ml or microg/g) of trichlorfon and methidathion were 409 and 1.9 in the heart blood, 281 and 0.4 in the femoral vein blood, 430 and 5.8 in the cerebrum, 385 and 5.1 in the brain stem, 256 and 2.8 in the right apex of lung, 449 and 15.1 in the left basal of lung, 856 and 131.0 in the liver, 460 and 1.6 in the right kidney, 390 and 1.9 in the left kidney, 524 and 3.4 in the spleen, 152 and 0.6 in the thigh muscle, 207 and 0.9 in the urine, 20,000 and 19,400 in the gastric contents, respectively. According to the autopsy finding and toxicological analysis, the cause of death was judged to be acute trichlorfon and methidathion poisoning.

Analysis of paraquat, diquat and two diquat metabolites in biological materials by high-performance liquid chromatography.

The determination of paraquat, diquat and two metabolites of diquat in biological materials was developed using high-performance liquid chromatography combined with UV and fluorescence detectors. Paraquat, diquat and internal standards (ethyl viologen and o-acetamidophenol) were detected by the UV detector. Diquat-monopyridone and diquat-dipyridone were monitored by the fluorescence detector. Paraquat, diquat, diquat-monopyridone and ethyl viologen were effectively extracted from blood, liver and brain, using a Sep-Pak C(18) cartridge. Diquat-dipyridone and o-acetamidophenol were extracted with methanol. Paraquat and diquat at a concentration range of 0.1-10 microg/ml (or g), and diquat-monopyridone and diquat-dipyridone at a concentration range of 0.01-1 microg/ml (or g) in biological material were determined with high accuracy and precision. The detection limits of paraquat, diquat, diquat-monopyridone and diquat-dipyridone were 1, 1, 0.02 and 0.02 ng, respectively, as an injection amount. This method was applied for toxicological examination of a case of suspected paraquat and diquat intoxication. The analysis of the metabolites of diquat was helpful for the estimation of the elapsed time from ingestion to death.

A fatal case considered to be due to cardiac arrhythmia associated with butane inhalation.

An autopsy case of a 14-year-old boy whose death is considered to be a result of cardiac arrhythmia after butane inhalation and sample preservation for butane analysis are reported. The electrocardiogram taken in the ambulance revealed ventricular fibrillation. There were no autopsy findings as to the cause of death. n-Butane, isobutane and propane were identified in the blood, brain and lung of the cadaver by headspace gas chromatography. Based on these results, the cause of death was concluded to be cardiac arrhythmia due to butane inhalation. As a follow-up, n-butane, isobutane and propane concentrations in the blood kept at -30 degrees C showed the unchanged values with a coefficient of variation of within 10% for 2 weeks.