RESUMEN
An autopsy for a suicidal case of a male in his 40s, who had died of poisoning due to ingestion of a large amount of buformin, was performed at our department. Buformin is biganide class agent used for patients of diabetes mellitus, which can occasionally cause severe lactic acidosis. The autopsy was performed about 10 days after his death, and the direct cause of his death was judged as asphyxia due to the aspiration of stomach contents into the airway. The nine body fluids and eight solid tissues specimens were dealt with for investigating postmortem distribution/redistribution of buformin in a whole body; femoral vein blood, right and left heart blood, pericardial fluid, urine, bile, stomach contents, small intestine contents, cerebrospinal fluid, the brain, lung, heart muscle, liver, spleen, kidney and skeletal muscle were examined. For extracting buformin from specimens, a modified QuEChERS method including dispersive solid-phase extraction was employed, followed by the analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). Buformin in various kinds of human matrices were quantified by the standard addition method in this study, which can overcome the matrix effects and recovery rates without use of blank human matrices. All concentrations of buformin in specimens examined in this case were extremely higher than those of previously reported poisoning cases. The concentrations of buformin in left and right heart blood and femoral vein blood specimens of this case were 399, 216 and 261µg/mL, respectively; although the direct cause of his death was judged as asphyxia due to occlusion of airway with stomach contents, the vomiting was thought to be provoked by buformin poisoning. In this study, marked differences of buformin concentrations between brain tissue and cerebral spiral fluids, and other specimens were observed, which suggested that its distribution was influenced also by blood-brain-barrier. Although a number of buformin poisoning cases were published so far, they gave sporadic data on its concentrations and/or distribution in some limited human specimens. This study is the first to describe detailed distribution/redistribution of buformin in a whole human body quantified by using LC-MS/MS.
Asunto(s)
Buformina/farmacocinética , Hipoglucemiantes/farmacocinética , Cambios Post Mortem , Adulto , Asfixia/etiología , Bilis/química , Química Encefálica , Buformina/análisis , Buformina/envenenamiento , Cromatografía Liquida , Sobredosis de Droga , Contenido Digestivo/química , Humanos , Hipoglucemiantes/análisis , Hipoglucemiantes/envenenamiento , Intestino Delgado/química , Riñón/química , Hígado/química , Pulmón/química , Masculino , Músculo Esquelético/química , Miocardio/química , Líquido Pericárdico/química , Aspiración Respiratoria/etiología , Extracción en Fase Sólida/métodos , Bazo/química , Espectrometría de Masas en TándemRESUMEN
A specific method is described for the quantitation of the oral hypoglycemic biguanide buformin in biological material by gas chromatography. Phenformin, another biguanide derivative, is used as internal standard. Both compounds are converted to the corresponding s-triazine derivatives by reacting with acetic anhydride prior to gas chromatography with nitrogen-specific detection. The described procedure has been applied to the quantitative assay of buformin in body fluids and tissues, obtained from a postmortem case. The results of these toxicological investigations are discussed.