Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in bile

  • L. Fanton
  • F. Bevalot
  • M. P. Gustin
  • C. Z. Paultre
  • C. Le Meur
  • D.  Malicier
Original Article

Abstract

Investigating toxicological causes of death may require alternative matrices when the usual ones are lacking. Whereas forensic toxicology uses bile almost only for xenobiotic screening, a diagnostic test interpreting postmortem bile concentrations of meprobamate is reported. Based on 128 sets of autopsy data, its intrinsic qualities were good, with 0.95 sensitivity and 0.93 specificity. In a French forensic population, the positive and negative predictive factors were 0.90 and 0.97, respectively. It is a useful means of revealing overdoses where blood samples are not available or of confirming blood tests when postmortem redistribution is suspected.

Keywords

Meprobamate Bile Forensic toxicology Lethal intoxication Autopsy 

References

  1. 1.
    Mangin P (2002) Autopsie médico-légale. Rev Prat 52:723–728PubMedGoogle Scholar
  2. 2.
    Pounder DJ, Jones GR (1990) Post-mortem drug redistribution—a toxicological nightmare. Forensic Sci Int 45:253–263PubMedCrossRefGoogle Scholar
  3. 3.
    De Letter EA, Lambert WE, Bouche MP, Cordonnier JA, Van Bocxlaer JF, Piette MH (2007) Postmortem distribution of 3,4-methylenedioxy-N,N-dimethyl-amphetamine (MDDM or MDDA) in a fatal MDMA overdose. Int J Legal Med 121:303–307PubMedCrossRefGoogle Scholar
  4. 4.
    Flanagan RJ (1998) Guidelines for the interpretation of analytical toxicology results and unit of measurement conversion factors. Ann Clin Biochem 35(Pt 2):261–267PubMedGoogle Scholar
  5. 5.
    TIAFT reference blood level list of therapeutic and toxic substances (2005) Available from: http://www.tiaft.org/. Cited July 2007 (database on the Internet)
  6. 6.
    Musshoff F, Padosch S, Steinborn S, Madea B (2004) Fatal blood and tissue concentrations of more than 200 drugs. Forensic Sci Int 142:161–210PubMedCrossRefGoogle Scholar
  7. 7.
    Agarwal A, Lemos N (1996) Significance of bile analysis in drug-induced deaths. J Anal Toxicol 20:61–63PubMedGoogle Scholar
  8. 8.
    Vanbinst R, Koenig J, Di Fazio V, Hassoun A (2002) Bile analysis of drugs in postmortem cases. Forensic Sci Int 128:35–40PubMedCrossRefGoogle Scholar
  9. 9.
    Winek CL, Esposito FM (1981) Comparative study of ethanol levels in blood versus bone marrow, vitreous humor, bile and urine. Forensic Sci Int 17:27–36PubMedCrossRefGoogle Scholar
  10. 10.
    Kugelberg FC, Jones AW (2007) Interpreting results of ethanol analysis in postmortem specimens: a review of the literature. Forensic Sci Int 165:10–29PubMedCrossRefGoogle Scholar
  11. 11.
    Kass K, Szlavik N, Klausz G, Rona K (2006) Epebol torteno etilalkohol meghatarozas jelentosege az igazsagugyi orvostani gyakorlatban (in Hungarian). Acta Pharm Hung 76:133–137PubMedGoogle Scholar
  12. 12.
    Bévalot F, Fanton L, Le Meur C, Malicier D (2005) Interpretation of biliary drug concentrations: case of cyamemazine, meprobamate and nordazepam. Proceeding of the 17Th Meeting of International Association of Forensic Sciences, Hong Kong, China p. 467Google Scholar
  13. 13.
    Felby S (1970) Concentrations of meprobamate in the blood and liver following fatal meprobamate poisoning. Acta Pharmacol Toxicol (Copenh) 28:334–337Google Scholar
  14. 14.
    Gaillard Y, Billault F, Pepin G (1997) Meprobamate overdosage: a continuing problem. Sensitive GC-MS quantitation after solid phase extraction in 19 fatal cases. Forensic Sci Int 86:173–180PubMedCrossRefGoogle Scholar
  15. 15.
    Osvath P, Fekete S (2003) A pszichofarmakonvalasztas jellemzoi ongyilkossagi kiserletekben (in Hungarian). Orv Hetil 144:121–124PubMedGoogle Scholar
  16. 16.
    Fanton L, Bevalot F, Schoendorff P, Le Meur C, Gaillard Y, Malicier D (2007) Fatal mephenesin intoxication. J Forensic Sci 52:221–223PubMedCrossRefGoogle Scholar
  17. 17.
    Maurer HH (1992) Systematic toxicological analysis of drugs and their metabolites by gas chromatography-mass spectrometry. J Chromatogr 580:3–41PubMedCrossRefGoogle Scholar
  18. 18.
    Fink H, Luppa P, Mayer B, Rosenbrock H, Metzger J, Martyn JA et al (2003) Systemic inflammation leads to resistance to atracurium without increasing membrane expression of acetylcholine receptors. Anesthesiology 98:82–88PubMedCrossRefGoogle Scholar
  19. 19.
    Peeters MY, Aarts LP, Boom FA, Bras LJ, Tibboel D, Danhof M et al (2008) Pilot study on the influence of liver blood flow and cardiac output on the clearance of propofol in critically ill patients. Eur J Clin Pharmacol 64:329–334PubMedCrossRefGoogle Scholar
  20. 20.
    Delco F, Tchambaz L, Schlienger R, Drewe J, Krahenbuhl S (2005) Dose adjustment in patients with liver disease. Drug Safety 28:529–545PubMedCrossRefGoogle Scholar
  21. 21.
    Angelin B, Arvidsson A, Dahlqvist R, Hedman A, Schenck-Gustafsson K (1987) Quinidine reduces biliary clearance of digoxin in man. Eur J Clin Invest 17:262–265PubMedCrossRefGoogle Scholar
  22. 22.
    Shitara Y, Sato H, Sugiyama Y (2005) Evaluation of drug-drug interaction in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol 45:689–723PubMedCrossRefGoogle Scholar
  23. 23.
    De Letter EA, Clauwaert KM, Belpaire FM, Lambert WE, Van Bocxlaer JF, Piette MH (2002) Post-mortem redistribution of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) in the rabbit. Part I: experimental approach after in vivo intravenous infusion. Int J Legal Med 116:216–224PubMedGoogle Scholar
  24. 24.
    Maes R, Hodnett N, Landesman H, Kananen G, Finkle B, Sunshine I (1969) The gas chromatographic determination of selected sedatives (ethchlorvynol, paraldehyde, meprobamate, and Carisoprodol) in biological material. J Forensic Sci 14:235–254PubMedGoogle Scholar
  25. 25.
    Kintz P, Tracqui A, Mangin P, Lugnier AA (1988) Fatal meprobamate self-poisoning. Am J Forensic Med Pathol 9:139–140PubMedCrossRefGoogle Scholar
  26. 26.
    Hoizey G, Canas F, Binet L, Bernard MH, Lamiable D (2007) Concentrations tissulaires post-mortem du méprobamate. Proceedings of the XVth meeting of the French Society of Analytical Toxicology (SFTA), Paris p. 72Google Scholar
  27. 27.
    Hoiseth G, Bramness JG, Christophersen AS, Morland J (2007) Carisoprodol intoxications: a retrospective study of forensic autopsy material from 1992–2003. Int J Legal Med 121:403–409PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • L. Fanton
    • 1
    • 2
  • F. Bevalot
    • 1
    • 2
    • 3
  • M. P. Gustin
    • 1
    • 4
  • C. Z. Paultre
    • 1
    • 4
  • C. Le Meur
    • 1
    • 2
    • 3
  • D.  Malicier
    • 1
    • 2
  1. 1.Université de LyonLyonFrance
  2. 2.Institut de Médecine LégaleUniversité Lyon 1LyonFrance
  3. 3.Institut de Médecine Légale, Unité de toxicologieUniversité Lyon 1LyonFrance
  4. 4.Institut des Sciences Pharmaceutiques et biologiques–ISPBUniversité Lyon 1LyonFrance

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