RESUMEN
A case of fatal suicidal bentazon poisoning is presented along with a description of the different analytical methods involved. A 56-year-old farmer was examined by the family doctor 1 h after voluntarily ingesting 500 mL of FIGHTER (bentazon, 480 g/L water). He presented a Glasgow score of 15, polypnea, diarrhea, and vomiting. During transport by ambulance to the hospital, he tossed, sweated, and suddenly presented breathing difficulty followed by heart failure. Tracheal intubation was impossible (H1.5) despite use of different diameter cannulas because of extreme general muscle rigidity. All attempts at resuscitation failed, and the patient died within 2 h postingestion. Blood and urine samples were taken just before death. General basic and neutral drug screening by high-performance liquid chromatography-diode-array detection and gas chromatography-nitrogen-phosphorus detection showed no strychnine or other drugs or toxics except for citalopram (< 0.1 mg/L) and bentazon, but this weak acidic molecule (pKa3.3) was badly extracted in alkaline conditions. Plasma and urine levels, measured after acidic extraction, protein precipitation, or simple dilution, were 1500 and 1000 mg/L, respectively. Bentazon (M.W. 240) was confirmed by its basic mass spectrum (ESI-, m/z 239, 197, 175, 132) or by that of methylated derivative (El+, m/z 254, 212, 175). An hydroxylated metabolite (ESI-, m/z 255, 213, 191, 148; El+, m/z 284, 242, 163) and the N1-glucuronide conjugate of bentazon (ESI-, m/z 415, 239) were also detected in urine. (Quantitation ions are underlined.) This first case of bentazon poisoning with available analytical data revealed the high toxicity of this compound after large dose ingestion with early and heavy symptoms such as muscle rigidity probably related to muscular toxicity. Comparison with another nonfatal case and with toxicological data on animals is discussed.
Asunto(s)
Benzotiadiazinas/envenenamiento , Herbicidas/envenenamiento , Suicidio , Benzotiadiazinas/sangre , Benzotiadiazinas/orina , Cromatografía Líquida de Alta Presión , Herbicidas/sangre , Herbicidas/orina , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study describes a matrix-assisted laser-desorption-ionization (MALDI) mass spectrometry for rapid screening of 12 diuretics in spiked urine. C60 is used as the matrix for MALDI. Diuretics are directly analyzed by C60-MALDI without previous derivatization. The fact that most diuretic molecules contain sulfate groups accounts for why anions of the molecules can be easily desorbed and ionized in MALDI. Using C60 as the matrix is advantageous because of the low background in the low mass range on the negative MALDI mass spectrum. A clear mass window between m/z 200 and 600 in negative ion mode is also obtained. Only a minimum amount of the sample (< 1 microL) is necessary to perform the analysis. The detection limit of diuretics is approximately 0.1-1 microg/mL.
Asunto(s)
Carbono/química , Diuréticos/orina , Fulerenos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Detección de Abuso de Sustancias/métodos , Benzotiadiazinas/orina , Humanos , Sensibilidad y Especificidad , Inhibidores de los Simportadores del Cloruro de Sodio/orinaRESUMEN
The effect of a single oral dose of 25 mg bemetizide on renal function without and with concomitant administration of the prostaglandin synthesis inhibitor indomethacin was investigated in ten healthy volunteers during sustained water diuresis. Bemetizide induced a significant increase in urinary sodium and chloride excretion from 196 +/- 30 and 163 +/- 28 mumol/min to 690 +/- 54 and 537 +/- 51 mumol/min (P less than 0.01). This effect occurred in the absence of changes in glomerular filtration rate, urinary excretion of phosphate or the delivery of chloride beyond the proximal nephron to the distal tubules (distal delivery) [(CH2O + CCl)/GFR . 100], but was associated with a significant decrease in distal fractional chloride absorption (DFACl) [CH2O/(CH2O + CCl)] from 0.84 +/- 0.02 to 0.63 +/- 0.02 (P less than 0.01). Bemetizide also increased urinary excretion of prostaglandin (PG) E2. Concomitant indomethacin administration significantly suppressed urinary excretion of PGE2 and markedly decreased urinary excretion of sodium and chloride during control and following bemetizide administration. Indomethacin had no effect on glomerular filtration rate, urinary excretion of phosphate, distal delivery or the urinary excretion of bemetizide but significantly increased DFACl both during control and after bemetizide administration. Our results show that bemetizide as a thiazide-diuretic acts in the diluting segments of the nephron. Indomethacin administration induces retention of sodium and chloride and blunts the renal effects of bemetizide via increased absorption in the diluting segments. The interaction of both drugs most likely represents a pharmacodynamic interaction.