Time-dependent postmortem redistribution of morphine and its metabolites in blood and alternative matrices-application of CT-guided biopsy sampling

Int J Legal Med. 2017 Mar;131(2):379-389. doi: 10.1007/s00414-016-1485-2. Epub 2016 Dec 3.

Abstract

Interpretation of postmortem morphine concentrations in forensic toxicology provides several pitfalls such as missing information on tolerance, analyte stability, or postmortem redistribution (PMR). Recently, it had been shown that computed tomography (CT)-guided collection of biopsies using a robotic arm (virtobot) provides a valuable strategy for systematic studies on time-dependent PMR. Using this technique, time-dependent PMR of morphine and its metabolites was investigated in 12 cases. At admission to the institute (t1), femoral and heart blood (right ventricle) as well as biopsies from the right lung, the right kidney, liver, spleen, and muscle tissue were collected. At autopsy approximately 24 h later (t2), samples from the same body regions were collected again. Additionally, gastric contents, urine, brain tissue, and heart blood from the left ventricle was collected. Morphine, normorphine, hydromorphone, morphine-3-glucuronide, morphine-6-glucuronide, and morphine-sulfate were quantified with LC-MS/MS. In femoral blood, significant increase of morphine concentrations was observed, although ultimately not relevant for forensic interpretation. In the alternative matrices, increases as well as decreases were observed without a clear trend. The morphine metabolites did not exhibit relevant concentration changes. Investigation of underlying redistribution mechanisms indicated that concentration change (i.e., increase) of morphine in femoral blood rather resulted from diffusion processes than from release of morphine from its conjugates. Concentration changes in heart blood might have been caused by redistribution from lung tissue or gastric content. This study also proved that CT-guided collection of biopsies using a virtobot arm is an invaluable tool for future studies on PMR redistribution of other substance groups.

Keywords: Alternative matrices; CT-guided biopsies; LC-MS/MS; Morphine; Time-dependent postmortem redistribution.

MeSH terms

  • Biopsy, Fine-Needle
  • Brain / diagnostic imaging
  • Brain Chemistry
  • Chromatography, Liquid
  • Gastrointestinal Contents / diagnostic imaging
  • Heart / diagnostic imaging
  • Humans
  • Kidney / chemistry
  • Kidney / diagnostic imaging
  • Liver / chemistry
  • Liver / diagnostic imaging
  • Lung / chemistry
  • Lung / diagnostic imaging
  • Mass Spectrometry
  • Morphine / blood*
  • Morphine / pharmacokinetics
  • Morphine Derivatives / blood*
  • Morphine Derivatives / pharmacokinetics
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / diagnostic imaging
  • Myocardium / chemistry
  • Narcotics / blood*
  • Narcotics / pharmacokinetics
  • Postmortem Changes*
  • Radiography, Interventional
  • Spleen / chemistry
  • Spleen / diagnostic imaging
  • Time Factors
  • Tomography, X-Ray Computed

Substances

  • Morphine Derivatives
  • Narcotics
  • Morphine