Skip to main content
Log in

The effect of the postmortem interval on the redistribution of drugs: a comparison of mortuary admission and autopsy blood specimens

  • Original Article
  • Published:
Forensic Science, Medicine, and Pathology Aims and scope Submit manuscript

Abstract

Postmortem redistribution (PMR) is an accepted toxicological phenomenon that may affect the interpretation of postmortem blood concentrations. The extent of PMR is not well understood for some drugs. This report describes the PMR of selected substances resulting from the analysis of 149 cases comparing blood specimens taken at admission of the deceased to the mortuary and then at autopsy. Blood was collected in preserved tubes containing 1 % sodium fluoride/potassium oxalate. All cases were subject to a full autopsy and blood extracts were analyzed using a targeted screen by LC–MS/MS. 30 drug or drug metabolites that were detected with an incidence of 6 or more were included in this study. The pre-autopsy interval ranged from 0.5 to 164 h (6.4 days) with an average of 64 h for the cases analyzed. The increase in drug concentration from mortuary admission to autopsy ranged from 30 % for drugs such as citalopram, mirtazapine, and sertraline to 300 % for doxylamine. Only 7 drugs of the 30 studied showed increases of greater than 20 % when comparing autopsy to mortuary admission blood irrespective of the length of the postmortem interval. Drugs including methadone, EDDP, fluoxetine, mirtazapine, and sertraline all showed statistically significant increases during the pre-autopsy interval (p < 0.05) while 6-acetylmorphine, 9-hydroxy-risperidone, and caffeine showed significant decreases (p < 0.05) from mortuary admission to autopsy. While femoral blood is thought to reduce PMR, this data shows that for some drugs significant redistribution can occur even when taking peripheral specimens irrespective of the delay in the postmortem interval.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

References

  1. Drummer OH, Gerostamoulos J. Postmortem drug analysis: analytical and toxicological aspects. Ther Drug Monit. 2002;24(2):199–209.

    Article  PubMed  CAS  Google Scholar 

  2. Yarema MC, Becker CE. Key concepts in postmortem drug redistribution. Clin Toxicol (Phila). 2005;43(4):235–41.

    CAS  Google Scholar 

  3. Ferner RE. Postmortem clinical pharmacology. Br J Clin Pharmacol. 2008;66(4):430–43.

    Article  PubMed  CAS  Google Scholar 

  4. Pélissier-Alicot AL, Gaulier JM, Champsaur P, Marquet P. Mechanisms underlying postmortem redistribution of drugs: a review. J Anal Toxicol. 2003;27(8):533–44.

    PubMed  Google Scholar 

  5. Skopp G. Postmortem toxicology. Forensic Sci Med Pathol. 2010;6(4):314–25.

    Article  PubMed  CAS  Google Scholar 

  6. Jones GR, Pounder DJ. Site dependence of drug concentrations in postmortem blood-a case study. J Anal Toxicol. 1987;11(5):186–90.

    PubMed  CAS  Google Scholar 

  7. Prouty RW, Anderson WH. A comparison of postmortem heart blood and femoral blood ethyl alcohol concentrations. J Anal Toxicol. 1987;11(5):191–7.

    PubMed  CAS  Google Scholar 

  8. Kuhlman JJ Jr, Mayes RW, Levine B, Jones R, Wagner GN, Smith ML. Chloroquine distribution in postmortem cases. J Forensic Sci. 1991;36(5):1572–9.

    PubMed  CAS  Google Scholar 

  9. Hilberg T, Mørland J, Bjørneboe A. Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution. Forensic Sci Int. 1994;64(1):47–55.

    Article  PubMed  CAS  Google Scholar 

  10. McIntyre IM, King CV, Cordner SM, Drummer OH. Postmortem clomipramine: therapeutic or toxic concentrations? J Forensic Sci. 1994;39(2):486–93.

    PubMed  CAS  Google Scholar 

  11. Pounder DJ, Hartley AK, Watmough PJ. Postmortem redistribution and degradation of dothiepin: human case studies and an animal model. Am J Forensic Med Pathol. 1994;15(3):231–5.

    Article  PubMed  CAS  Google Scholar 

  12. Logan BK, Smirnow D. Postmortem distribution and redistribution of morphine in man. J Forensic Sci. 1996;41(2):221–9.

    PubMed  CAS  Google Scholar 

  13. Pohland RC, Bernhard NR. Postmortem serum and tissue redistribution of fluoxetine and norfluoxetine in dogs following oral administration of fluoxetine hydrochloride (Prozac®). J Forensic Sci. 1997;42(5):812–6.

    PubMed  CAS  Google Scholar 

  14. Robertson MD, Drummer OH. Postmortem distribution and redistribution of nitrobenzodiazepines in man. J Forensic Sci. 1998;43(1):9–13.

    PubMed  CAS  Google Scholar 

  15. Barnhart FE, Fogacci JR, Reed DW. Methamphetamine—a study of postmortem redistribution. J Anal Toxicol. 1999;23(1):69–70.

    PubMed  CAS  Google Scholar 

  16. Couper FJ, Drummer OH. Postmortem stability and interpretation of β2-agonist concentrations. J Forensic Sci. 1999;44(3):523–6.

    PubMed  CAS  Google Scholar 

  17. Jaffe PD, Batziris HP, van der Hoeven P, et al. A study involving venlafaxine overdoses: comparison of fatal and therapeutic concentrations in postmortem specimens. J Forensic Sci. 1999;44(1):193–6.

    PubMed  CAS  Google Scholar 

  18. Kunsman GW, Rodriguez R, Rodriguez P. Fluvoxamine distribution in postmortem cases. Am J Forensic Med Pathol. 1999;20(1):78–83.

    Article  PubMed  CAS  Google Scholar 

  19. Gerostamoulos J, Drummer OH. Postmortem redistribution of morphine and its metabolites. J Forensic Sci. 2000;45(4):843–5.

    PubMed  CAS  Google Scholar 

  20. Kerswill RM, Vicente MR. Clozapine and postmortem redistribution. Am J Psychiatry. 2003;160(1):184.

    Article  PubMed  Google Scholar 

  21. Rodda KE, Drummer OH. The redistribution of selected psychiatric drugs in postmortem cases. Forensic Sci Int. 2006;164(2–3):235–9.

    Article  PubMed  CAS  Google Scholar 

  22. Olson KN, Luckenbill K, Thompson J, Middleton O, Geiselhart R, Mills KM, Kloss J, Apple FS. Postmortem redistribution of fentanyl in blood. Am J Clin Pathol. 2010;133(3):447–53.

    Article  PubMed  CAS  Google Scholar 

  23. Moriya F, Hashimoto Y. Pericardial fluid as an alternative specimen to blood for postmortem toxicological analyses. Legal Med. 1999;1(2):86–94.

    Article  PubMed  CAS  Google Scholar 

  24. Moriya F, Hashimoto Y. Redistribution of basic drugs into cardiac blood from surrounding tissues during early-stages postmortem. J Forensic Sci. 1999;44(1):10–6.

    PubMed  CAS  Google Scholar 

  25. Yarema MC, Becker CE. Key concepts in postmortem drug redistribution. Clin Toxicol. 2005;43(4):235–41.

    CAS  Google Scholar 

  26. Pelissier-Alicot AL, Coste N, Bartoli C, Piercecchi-Marti MD, Sanvoisin A, Gouvernet J, Leonetti G. Comparison of ethanol concentrations in right cardiac blood, left cardiac blood and peripheral blood in a series of 30 cases. Forensic Sci Int. 2006;156(1):35–9.

    Article  PubMed  CAS  Google Scholar 

  27. Pok PRP, Haddouche D, Mauras M, Kuhlmann E, Burle J, Salmon T, Berland E, Coiffait PE, Viala A. Cardiac and peripheral blood similarities in the comparison of nordiazepam and bromazepam blood concentrations. J Anal Toxicol. 2008;32(9):782–6.

    Google Scholar 

  28. Drummer OH. Forensic toxicology. EXS. 2010;100:579–603.

    Google Scholar 

  29. Prouty RW, Anderson WH. The forensic science implications of site and temporal influences on postmortem blood-drug concentrations. J Forensic Sci. 1990;35(2):243–70.

    PubMed  CAS  Google Scholar 

  30. Butzbach DM. The influence of putrefaction and sample storage on postmortem toxicology results. Forensic Sci Med Pathol. 2010;6(1):35–45.

    Article  PubMed  Google Scholar 

  31. Hearn WL, Keran EE, Huang W, Hime G. Site-dependent postmortem changes in blood cocaine concentrations. J Forensic Sci. 1991;36(3):673–84.

    PubMed  CAS  Google Scholar 

  32. Saar E, Gerostamoulos D, Dummer OH, et al. Identification and quantification of 30 antipsychotics in blood using LC-MS/MS. J Mass Spectrom. 2010;45(8):915–25.

    Article  PubMed  CAS  Google Scholar 

  33. Cook DS, Braithwaite RA, Hale KA. Estimating antemortem drug concentrations from postmortem blood samples: the influence of postmortem redistribution. J Clin Pathol. 2000;53(4):282–5.

    Article  PubMed  CAS  Google Scholar 

  34. Drummer O, Forrest AR, Goldberger B, Karch SB. Forensic science in the dock. BMJ. 2004;329(7467):636–7.

    Article  PubMed  Google Scholar 

  35. Karch SB. Is postmortem toxicology quackery? J Clin Forensic Med. 2003;10(3):197–8.

    Article  PubMed  Google Scholar 

  36. Flanagan RJ, Connally G, Evans JM. Analytical toxicology: guidelines for sample collection postmortem. Toxicol Rev. 2005;24(1):63–71.

    Article  PubMed  CAS  Google Scholar 

  37. Forrest AR. ACP Broadsheet no 137: April 1993. Obtaining samples at post mortem examination for toxicological and biochemical analyses. J Clin Pathol. 1993;46(4):292–6.

    Article  PubMed  CAS  Google Scholar 

  38. Kennedy MC. Postmortem drug concentrations. Intern Med J. 2010;40(3):183–7.

    Article  PubMed  CAS  Google Scholar 

  39. Dinis-Oliveira RJ, Carvalho F, Duarte JA, et al. Collection of biological samples in forensic toxicology. Toxicol Mech Methods. 2010;20(7):363–414.

    Article  PubMed  CAS  Google Scholar 

  40. Drummer OH. Postmortem toxicology of drugs of abuse. Forensic Sci Int. 2004;142(2–3):101–13.

    Article  PubMed  CAS  Google Scholar 

  41. Skopp G. Preanalytic aspects in postmortem toxicology. Forensic Sci Int. 2004;142(2–3):75–100.

    Article  PubMed  CAS  Google Scholar 

  42. Drummer OH. Postmortem toxicology. Forensic Sci Int. 2007;165(2–3):199–203.

    Article  PubMed  CAS  Google Scholar 

  43. Hepler BR, Isenschmid DS, Schmidt CJ. postmortem redistribution: practical considerations in death investigation, presented at the American Academy of Forensic Sciences: Dallas: 2004. Abstract K-14.

  44. Rohrig TP, Prouty RW. Fluoxetine overdose: a case report. J Anal Toxicol. 1989;13(5):305–7.

    PubMed  CAS  Google Scholar 

  45. Rohrig TP, Prouty RW. A nortriptyline death with unusually high tissue concentrations. J Anal Toxicol. 1989;13(5):303–4.

    PubMed  CAS  Google Scholar 

  46. Anderson DT, Fritz KL, Muto JJ. Distribution of mirtazapine (Remeron) in thirteen postmortem cases. J Anal Toxicol. 1999;23(6):544–8.

    PubMed  CAS  Google Scholar 

  47. Levine B, Jenkins AJ, Smialek JE. Distribution of sertraline in postmortem cases. J Anal Toxicol. 1994;18(5):272–4.

    PubMed  CAS  Google Scholar 

  48. Tolliver SSH, Lee W, Furton KG. Evaluating the relationship between postmortem and antemortem morphine and codeine concentrations in whole blood. J Anal Toxicol. 2010;34:491–7.

    PubMed  CAS  Google Scholar 

  49. Gerostamoulos J, Burke MP, Drummer OH. Involvement of codeine in drug-related deaths. Am J Forensic Med Pathol. 1996;17(4):327–35.

    Article  PubMed  CAS  Google Scholar 

  50. Sousa T, Paterson R, Moore V, Carlsson A, Abrahamsson B, Basit AW. The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm. 2008;363(1–2):1–25.

    Article  PubMed  CAS  Google Scholar 

  51. Karch S. Response to postcard from Sweden. J Forensic Leg Med. 2009;16(8):501–2.

    Article  PubMed  Google Scholar 

  52. Carroll FT, Marraccini JV, Lewis S, Wright W. Morphine-3-d glucuronide stability in postmortem specimens exposed to bacterial enzymatic hydrolysis. Am J Forensic Med Pathol. 2000;21(4):323–9.

    Article  PubMed  CAS  Google Scholar 

  53. Rook EJ, Huitema ADR, van den Brink W, van Ree JM, Beijnen JH. Pharmacokinetics and pharmacokinetic variability of heroin and its metabolites: review of the literature. Curr Clin Pharmacol. 2006;1(1):109–18.

    Article  PubMed  CAS  Google Scholar 

  54. Peters FT, Schaefer S, Staack RF, et al. Screening for and validated quantification of amphetamines and of amphetamine- and piperazine-derived designer drugs in human blood plasma by gas chromatography/mass spectrometry. J Mass Spectrom. 2003;38(6):659–76.

    Article  PubMed  CAS  Google Scholar 

  55. Holmgren P, Druid H, Holmgren A, et al. Stability of drugs in stored postmortem femoral blood and vitreous humor. J Forensic Sci. 2004;49(4):820–5.

    Article  PubMed  CAS  Google Scholar 

  56. Stevens HM. The stability of some drugs and poisons in putrefying human liver tissues. J Forensic Sci Soc. 1984;24(6):577–89.

    Article  PubMed  CAS  Google Scholar 

  57. Saukko PJ, Knight B. Knight’s forensic pathology. 3rd ed. London: Arnold; 2004.

    Google Scholar 

  58. Robertson MD, Drummer OH. Postmortem drug metabolism by bacteria. J Forensic Sci. 1995;40(3):382–6.

    PubMed  CAS  Google Scholar 

  59. Giaginis C, Tsantili-Kakoulidou A, Theocharis S. Quantitative structure-activity relationship (QSAR) methodology in forensic toxicology: modeling postmortem redistribution of structurally diverse drugs using multivariate statistics. Forensic Sci Int. 2009;190(1–3):9–15.

    Article  PubMed  CAS  Google Scholar 

  60. Jones GR, Peat MA. Forensic toxicology laboratory guidelines. J Anal Toxicol. 1999;23(7):636.

    PubMed  CAS  Google Scholar 

  61. Hargrove VM, McCutcheon JR. Comparison of drug concentrations taken from clamped and unclamped femoral vessels. J Anal Toxicol. 2008;32(8):621–5.

    PubMed  CAS  Google Scholar 

  62. Hilberg T, Bugge A, Beylich KM, Mørland J, Bjørneboe A. Diffusion as a mechanism of postmortem drug redistribution: an experimental study in rats. Int J Legal Med. 1992;105(2):87–91.

    Article  PubMed  CAS  Google Scholar 

  63. Caplehorn JR, Drummer OH. Methadone dose and postmortem blood concentration. Drug Alcohol Rev. 2002;21(4):329–33.

    Article  PubMed  Google Scholar 

  64. Baselt RC. Disposition of toxic drugs and chemicals in man. 9th ed. Seal Beach: Biomedical Publications; 2011.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dimitri Gerostamoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerostamoulos, D., Beyer, J., Staikos, V. et al. The effect of the postmortem interval on the redistribution of drugs: a comparison of mortuary admission and autopsy blood specimens. Forensic Sci Med Pathol 8, 373–379 (2012). https://doi.org/10.1007/s12024-012-9341-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12024-012-9341-2

Keywords

Navigation