Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colchicine overdose is uncommon but potentially life threatening because of the high toxicity of the drug. Poisoning by colchicine may occur following ingestion of medication used in acute attacks of gout and inflammatory diseases. We describe two cases involving suicide by the ingestion of medications marketed in France. In case 1, only heart blood was taken after body external examination. In case 2 an autopsy was performed and heart blood, urine, gastric contents and bile were taken for toxicological analysis. Colchicine was assayed in biological specimens by an HPLC-DAD method, after extraction by dichloromethane at pH 8, adding prazepam as internal standard (IS). Analyses were performed on a Symetry C-8 column. Mobile phase was a gradient of acetonitrile/pH 3.8 phosphate buffer. Colchicine is eluted at 13.1 min and the method is linear for blood, urine and bile over the range 4-1000 ng/mL. LOQ is 4 ng/mL. The concentrations of colchicine detected are: case 1: heart blood 13 ng/mL; case 2: heart blood 66 ng/mL, urine 500 ng/mL, gastric content 12 ng/mL, bile 5632 ng/mL. Our findings are in the range of lethal concentrations previously described, but there is no correlation with the amount of ingested drug. Even after massive overdose, it could be impossible to detect colchicine in blood, and as there is a widespread enterohepatic recirculation before excretion in bile and feces, bile is the target sample to analyse. We conclude in both cases that the cause of death was suicide with colchicine. It appears very important to perform an autopsy in order to obtain bile, urine, heart blood and femoral blood.
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PMID:Colchicine poisoning: case report of two suicides. 1524 48

Poisoning by colchicine may occur following ingestion of this alkaloid used for the treatment of acute gouty arthritis. The authors report two fatalities and describe a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) triple-quadrupole method for the determination of colchicine in autopsy samples. One milliliter of heart blood, femoral blood, urine, bile, gastric, and vitreous each were extracted with saturated NH4Cl at pH 9.6 and dichloromethane/5% isopropanol. Separation was achieved on a C18-Xterra column with a mobile phase consisting of 2 mM ammonium formate buffer (pH 3)/acetonitrile in a gradient mode. Four product ions of the protonated molecule were monitored. The method was fully validated in whole blood (1 mL) and was linear in the range of 0.5-50 ng/mL (r2>0.99). The limit of detection was 0.1 ng/mL (50 times S/N), and the limit of quantitation was 0.5 ng/mL with RSDs<11.8% intraday (n=6), <18.7% interday (n=18), and accuracy<3% (n=18). Case #1: a 33-year-old nurse committed suicide by the ingestion of 80 colchicine 1-mg tablets. She died 61 h later after resuscitation procedures. Colchicine was found in heart blood at 5.2 ng/mL, femoral blood at 17.4 ng/mL, urine at 19.4 ng/mL, bile at 42.8 ng/mL, gastric at 348 ng/mL, and vitreous at 3 ng/mL. Case #2: a 57-year-old man with gout was found dead at home. Colchicine was found in heart blood at 22.8 ng/mL, femoral blood at 21.9 ng/mL, lung blood at 45.2 ng/mL, urine at 148.5 ng/mL, bile at 1818.5 ng/mL, gastric at 219.8 ng/mL, and vitreous at 0.5 ng/mL. These results were consistent with death. Because of its good sensitivity, this LC-ESI-MS-MS triple-quadrupole method is suitable for the determination of colchicine not only in fatalities but also for pharmacokinetic studies.
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PMID:Liquid chromatography-tandem mass spectrometry for the determination of colchicine in postmortem body fluids. Case report of two fatalities and review of the literature. 1713 57