Skip to main content
Top
Published in: International Journal of Legal Medicine 2/2017

01-03-2017 | Original Article

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

Authors: Sandra N. Staeheli, Dominic Gascho, Lars C. Ebert, Thomas Kraemer, Andrea E. Steuer

Published in: International Journal of Legal Medicine | Issue 2/2017

Login to get access

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.
Literature
1.
go back to reference Moriya F, Hashimoto Y (1997) Distribution of free and conjugated morphine in body fluids and tissues in a fatal heroin overdose: is conjugated morphine stable in postmortem specimens? J Forensic Sci 42(4):736–740CrossRefPubMed Moriya F, Hashimoto Y (1997) Distribution of free and conjugated morphine in body fluids and tissues in a fatal heroin overdose: is conjugated morphine stable in postmortem specimens? J Forensic Sci 42(4):736–740CrossRefPubMed
2.
go back to reference Pelissier-Alicot AL, Gaulier JM, Champsaur P, Marquet P (2003) Mechanisms underlying postmortem redistribution of drugs: a review. J Anal Toxicol 27(8):533–544CrossRefPubMed Pelissier-Alicot AL, Gaulier JM, Champsaur P, Marquet P (2003) Mechanisms underlying postmortem redistribution of drugs: a review. J Anal Toxicol 27(8):533–544CrossRefPubMed
3.
go back to reference Carroll FT, Marraccini JV, Lewis S, Wright W (2000) Morphine-3-D glucuronide stability in postmortem specimens exposed to bacterial enzymatic hydrolysis. Am J Forensic Med Pathol 21(4):323–329CrossRefPubMed Carroll FT, Marraccini JV, Lewis S, Wright W (2000) Morphine-3-D glucuronide stability in postmortem specimens exposed to bacterial enzymatic hydrolysis. Am J Forensic Med Pathol 21(4):323–329CrossRefPubMed
4.
go back to reference Skopp G, Potsch L, Klingmann A, Mattern R (2001) Stability of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in fresh blood and plasma and postmortem blood samples. J Anal Toxicol 25(1):2–7CrossRefPubMed Skopp G, Potsch L, Klingmann A, Mattern R (2001) Stability of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in fresh blood and plasma and postmortem blood samples. J Anal Toxicol 25(1):2–7CrossRefPubMed
5.
go back to reference Skopp G, Lutz R, Potsch L, Ganssmann B, Klinder K, Schmidt A, Aderjan R, Mattern R (1997) An in vitro experiment for postmortem vascular permeation. The passage of morphine and morphine glucuronides across a vascular wall. J Forensic Sci 42(3):486–491CrossRefPubMed Skopp G, Lutz R, Potsch L, Ganssmann B, Klinder K, Schmidt A, Aderjan R, Mattern R (1997) An in vitro experiment for postmortem vascular permeation. The passage of morphine and morphine glucuronides across a vascular wall. J Forensic Sci 42(3):486–491CrossRefPubMed
6.
go back to reference Skopp G, Lutz R, Ganssmann B, Mattern R, Aderjan R (1996) Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose. Int J Legal Med 109(3):118–124CrossRefPubMed Skopp G, Lutz R, Ganssmann B, Mattern R, Aderjan R (1996) Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose. Int J Legal Med 109(3):118–124CrossRefPubMed
7.
go back to reference Sawyer WR, Forney RB (1988) Postmortem disposition of morphine in rats. Forensic Sci Int 38(3–4):259–273CrossRefPubMed Sawyer WR, Forney RB (1988) Postmortem disposition of morphine in rats. Forensic Sci Int 38(3–4):259–273CrossRefPubMed
8.
go back to reference Koren G, Klein J (1992) Postmortem redistribution of morphine in rats. Ther Drug Monit 14(6):461–463CrossRefPubMed Koren G, Klein J (1992) Postmortem redistribution of morphine in rats. Ther Drug Monit 14(6):461–463CrossRefPubMed
9.
go back to reference Crandall CS, Kerrigan S, Aguero RL, Lavalley J, McKinney PE (2006) The influence of collection site and methods on postmortem morphine concentrations in a porcine model. J Anal Toxicol 30(9):651–658CrossRefPubMed Crandall CS, Kerrigan S, Aguero RL, Lavalley J, McKinney PE (2006) The influence of collection site and methods on postmortem morphine concentrations in a porcine model. J Anal Toxicol 30(9):651–658CrossRefPubMed
10.
go back to reference Maskell PD, Albeishy M, De Paoli G, Wilson NE, Seetohul LN (2015) Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h. Int J Legal Med 130(2):519–531CrossRefPubMed Maskell PD, Albeishy M, De Paoli G, Wilson NE, Seetohul LN (2015) Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h. Int J Legal Med 130(2):519–531CrossRefPubMed
11.
go back to reference Hargrove VM, Molina DK (2014) Peripheral postmortem redistribution of morphine. Am J Forensic Med Pathol 35(2):106–108CrossRefPubMed Hargrove VM, Molina DK (2014) Peripheral postmortem redistribution of morphine. Am J Forensic Med Pathol 35(2):106–108CrossRefPubMed
12.
go back to reference Gerostamoulos J, Drummer OH (2000) Postmortem redistribution of morphine and its metabolites. J Forensic Sci 45(4):843–845CrossRefPubMed Gerostamoulos J, Drummer OH (2000) Postmortem redistribution of morphine and its metabolites. J Forensic Sci 45(4):843–845CrossRefPubMed
13.
go back to reference Gerostamoulos D, Beyer J, Staikos V, Tayler P, Woodford N, Drummer OH (2012) 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(4):373–379CrossRefPubMed Gerostamoulos D, Beyer J, Staikos V, Tayler P, Woodford N, Drummer OH (2012) 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(4):373–379CrossRefPubMed
14.
go back to reference Logan BK, Smirnow D (1996) Postmortem distribution and redistribution of morphine in man. J Forensic Sci 41(2):221–229PubMed Logan BK, Smirnow D (1996) Postmortem distribution and redistribution of morphine in man. J Forensic Sci 41(2):221–229PubMed
15.
go back to reference Tolliver SS, Hearn WL, Furton KG (2010) Evaluating the relationship between postmortem and antemortem morphine and codeine concentrations in whole blood. J Anal Toxicol 34(8):491–497CrossRefPubMed Tolliver SS, Hearn WL, Furton KG (2010) Evaluating the relationship between postmortem and antemortem morphine and codeine concentrations in whole blood. J Anal Toxicol 34(8):491–497CrossRefPubMed
16.
go back to reference Staeheli SN, Gascho D, Fornaro J, Laberke P, Ebert LC, Martinez RM, Thali MJ, Kraemer T, Steuer AE (2016) Development of CT-guided biopsy sampling for time-dependent postmortem redistribution investigations in blood and alternative matrices-proof of concept and application on two cases. Anal Bioanal Chem 408(4):1249–1258CrossRefPubMed Staeheli SN, Gascho D, Fornaro J, Laberke P, Ebert LC, Martinez RM, Thali MJ, Kraemer T, Steuer AE (2016) Development of CT-guided biopsy sampling for time-dependent postmortem redistribution investigations in blood and alternative matrices-proof of concept and application on two cases. Anal Bioanal Chem 408(4):1249–1258CrossRefPubMed
17.
go back to reference Ebert LC, Ptacek W, Breitbeck R, Furst M, Kronreif G, Martinez RM, Thali M, Flach PM (2014) Virtobot 2.0: the future of automated surface documentation and CT-guided needle placement in forensic medicine. Forensic Sci Med Pathol 10(2):179–186CrossRefPubMed Ebert LC, Ptacek W, Breitbeck R, Furst M, Kronreif G, Martinez RM, Thali M, Flach PM (2014) Virtobot 2.0: the future of automated surface documentation and CT-guided needle placement in forensic medicine. Forensic Sci Med Pathol 10(2):179–186CrossRefPubMed
18.
go back to reference Staeheli SN, Poetzsch M, Kraemer T, Steuer AE (2015) Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional (13)C isotope monitoring. Anal Bioanal Chem 407(29):8681–8712CrossRefPubMed Staeheli SN, Poetzsch M, Kraemer T, Steuer AE (2015) Development and validation of a dynamic range-extended LC-MS/MS multi-analyte method for 11 different postmortem matrices for redistribution studies applying solvent calibration and additional (13)C isotope monitoring. Anal Bioanal Chem 407(29):8681–8712CrossRefPubMed
19.
go back to reference Taylor K, Elliott S (2009) A validated hybrid quadrupole linear ion-trap LC-MS method for the analysis of morphine and morphine glucuronides applied to opiate deaths. Forensic Sci Int 187(1–3):34–41CrossRefPubMed Taylor K, Elliott S (2009) A validated hybrid quadrupole linear ion-trap LC-MS method for the analysis of morphine and morphine glucuronides applied to opiate deaths. Forensic Sci Int 187(1–3):34–41CrossRefPubMed
20.
go back to reference Andersson M, Bjorkhem-Bergman L, Ekstrom L, Bergqvist L, Lagercrantz H, Rane A, Beck O (2014) Detection of morphine-3-sulfate and morphine-6-sulfate in human urine and plasma, and formation in liver cytosol. Pharmacol Res Perspect 2(6):e00071CrossRefPubMedPubMedCentral Andersson M, Bjorkhem-Bergman L, Ekstrom L, Bergqvist L, Lagercrantz H, Rane A, Beck O (2014) Detection of morphine-3-sulfate and morphine-6-sulfate in human urine and plasma, and formation in liver cytosol. Pharmacol Res Perspect 2(6):e00071CrossRefPubMedPubMedCentral
21.
go back to reference Wyman J, Bultman S (2004) Postmortem distribution of heroin metabolites in femoral blood, liver, cerebrospinal fluid, and vitreous humor. J Anal Toxicol 28(4):260–263CrossRefPubMed Wyman J, Bultman S (2004) Postmortem distribution of heroin metabolites in femoral blood, liver, cerebrospinal fluid, and vitreous humor. J Anal Toxicol 28(4):260–263CrossRefPubMed
22.
go back to reference Baselt RC (2008) Disposition of toxic drugs and chemicals in man, 8th edn. Chemical Toxicology Institute, Foster City Baselt RC (2008) Disposition of toxic drugs and chemicals in man, 8th edn. Chemical Toxicology Institute, Foster City
23.
go back to reference Pounder DJ, Smith DR (1995) Postmortem diffusion of alcohol from the stomach. Am J Forensic Med Pathol 16(2):89–96CrossRefPubMed Pounder DJ, Smith DR (1995) Postmortem diffusion of alcohol from the stomach. Am J Forensic Med Pathol 16(2):89–96CrossRefPubMed
24.
go back to reference Han E, Kim E, Hong H, Jeong S, Kim J, In S, Chung H, Lee S (2012) Evaluation of postmortem redistribution phenomena for commonly encountered drugs. Forensic Sci Int 219(1–3):265–271CrossRefPubMed Han E, Kim E, Hong H, Jeong S, Kim J, In S, Chung H, Lee S (2012) Evaluation of postmortem redistribution phenomena for commonly encountered drugs. Forensic Sci Int 219(1–3):265–271CrossRefPubMed
25.
go back to reference Carrupt PA, Testa B, Bechalany A, el Tayar N, Descas P, Perrissoud D (1991) Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity. J Med Chem 34(4):1272–1275CrossRefPubMed Carrupt PA, Testa B, Bechalany A, el Tayar N, Descas P, Perrissoud D (1991) Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity. J Med Chem 34(4):1272–1275CrossRefPubMed
Metadata
Title
Time-dependent postmortem redistribution of morphine and its metabolites in blood and alternative matrices—application of CT-guided biopsy sampling
Authors
Sandra N. Staeheli
Dominic Gascho
Lars C. Ebert
Thomas Kraemer
Andrea E. Steuer
Publication date
01-03-2017
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Legal Medicine / Issue 2/2017
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI
https://doi.org/10.1007/s00414-016-1485-2

Other articles of this Issue 2/2017

International Journal of Legal Medicine 2/2017 Go to the issue