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2019 10 31 Chemistry of Death Rebroadcast Slides
2019 10 31 Chemistry of Death Rebroadcast Slides
Postmortem
Redistribution
in Forensic
Toxicology
This ACS Webinar is a special rebroadcast of a past recording, there will be no slides available or interactive Q&A.
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Me
Me
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• Drug Chemistry
• Drug Pharmacokinetics
• Distribution Mechanisms
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• Lipophilicity
What is pKa?
• It is derived from Ka which is the equilibrium constant for the
chemical reaction known as dissociation in the context of acid-
base reactions
• pKa = - log10Ka
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• pKa = - log10Ka
Strong Base
• pKa is used in practice to avoid the many
orders of magnitude spanned by Ka
• It's also handy when you are trying to extract on the bench!
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• 30%
• 50%
• 75%
Me
• 90.1%
• 99.9% Me
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• 30%
• 50%
• 75%
Me
• 90.1%
• 99.9% Me
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Imipramine:
280 Da (Daltons)
Formula: C19H24N2
https://commons.wikimedia.org/wiki/File:Imipramine-3D-balls.png
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7,000 Da (Daltons)
Formula: C299H476N90O87S10
https://commons.wikimedia.org/wiki/File:3D
_model_of_calciseptine_structure.png
Drug Chemistry
• Protein Binding
• Volume of Distribution
• Storage Depots
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• Passive Transport
• Facilitated Diffusion
Adenosine triphosphate, also known as ATP, is a molecule that carries energy within cells. It is the main energy
currency of the cell, and it is an end product of the processes of photophosphorylation (adding a phosphate group
to a molecule using energy from light), cellular respiration, and fermentation.
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Vd is determined experimentally
𝑨𝒑
𝑽𝒅 =
𝑪𝒑
Imipramine has a Vd of 20 - 40 L/kg
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• Liver
• Brain
• Bone
• Hair
• Tongue
Image Credit: https://theodoregray.com/periodictable/Samples/082.27/index.s15.html
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• Liver
• Brain
• Bone
• Hair
• Tongue
Image Credit: https://theodoregray.com/periodictable/Samples/082.27/index.s15.html
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High PMR
low PMR
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• Digestion stops
• Breathing stops
• Metabolism stops
• Decomposition starts
• Blood flow stops
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https://www.researchgate.net/figure/Network-Topology-of-the-anaerobic-
glycolysis-A-and-aerobic-glycolysisB-v-ug-lumped_fig1_294059422
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• Lysosomal enzymes leak out, become active, and digest cell components and
membranes
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• “Micro” Redistribution
• Acidification
• Passive Diffusion
• Postmortem “Circulation”
• Putrefaction
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40 mg/L Tissue
1 mg/L Blood
Tissue
Time Zero
20 mg/L Tissue
10 mg/L Blood
Tissue
4 hours later
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Organs which are close to the heart and major blood vessels
• Liver (Left Lobe)
• Stomach / Esophagus
• Adipose Tissue
• Lungs
• Myocardium
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• “New” blood sources may pool near tissues and allow more
diffusion to occur
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- Slows redistribution
- Slows putrefaction
• Vitreous Humor
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• Take blood and tissue from specific sites
during autopsy
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• Lung
• Cerebrospinal fluid
• Bone Marrow
• Skeletal Muscle
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Cocaine 1.3
Imipramine 1.8
of sleeping problems.
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reference literature
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vs
Natural Postmortem
Reference
Ethanol (g/100mL) Imipramine (mg/L)
Tissue
Blood 0.42 - 1.77 6 - 8.5
Intoxication Fatality
Reference
Ethanol (g/100mL) Imipramine (mg/L)
Tissue
Blood 0.02 - 0.50 < 0.5
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1. Bynum ND, Poklis JL, Gaffney-Kraft M, Garside D, Ropero-Miller JD. Postmortem distribution of tramadol, amitriptyline, and their metabolites
in a suicidal overdose J Anal Toxicol. 2005;29(5):401-406.
2. Dinis-Oliveira RJ, Carvalho F, Duarte JA, et al. Collection of biological samples in forensic toxicology. Toxicol Mech Methods.
2010;20(7):363-414.
3. Gilliland MG, Bost RO. Alcohol in decomposed bodies: Postmortem synthesis and distribution J Forensic Sci. 1993;38(6):1266-1274.
4. Hargrove VM, McCutcheon JR. Comparison of drug concentrations taken from clamped and unclamped femoral vessels J Anal Toxicol.
2008;32(8):621-625.
5. Hebb JH,Jr, Caplan YH, Crooks CR, Mergner WJ. Blood and tissue concentrations of tricyclic antidepressant drugs in post mortem cases:
Literature survey and a study of forty deaths J Anal Toxicol. 1982;6(5):209-216.
6. Hilberg T, Ripel A, Slordal L, Bjorneboe A, Morland J. The extent of postmortem drug redistribution in a rat model J Forensic Sci.
1999;44(5):956-962.
7. Jones GR, Pounder DJ. Site dependence of drug concentrations in postmortem blood--a case study J Anal Toxicol. 1987;11(5):186-190.
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8. Langford AM, Pounder DJ. Possible markers for postmortem drug redistribution. J Forensic Sci. 1997;42(1):88-92.
9. Leikin JB, Watson WA. Post-mortem toxicology: What the dead can and cannot tell us J Toxicol Clin Toxicol. 2003;41(1):47-56.
10. Logan BK, Smirnow D. Postmortem distribution and redistribution of morphine in man. J Forensic Sci. 1996;41(2):221-229.
11. O'Sullivan JJ, McCarthy PT, Wren C. Differences in amiodarone, digoxin, flecainide and sotalol concentrations between
antemortem serum and femoral postmortem blood Hum Exp Toxicol. 1995;14(7):605-608.
12. Pelissier-Alicot A-, Gaulier J-, Champsaur P, Marquet P. Mechanisms underlying postmortem redistribution of drugs: A review J
Anal Toxicol. 2003;27(8):533 <last_page> 544. doi: 10.1093/jat/27.8.533.
13. Pounder DJ. The nightmare of postmortem drug changes Leg Med. 1993:163-191.
14. Pounder DJ, Jones GR. Post-mortem drug redistribution--a toxicological nightmare Forensic Sci Int. 1990;45(3):253-263.
15. Prouty RW, Anderson WH. The forensic science implications of site and temporal influences on postmortem blood-drug
concentrations J Forensic Sci. 1990;35(2):243-270.
16. Prouty RW, Anderson WH. A comparison of postmortem heart blood and femoral blood ethyl alcohol concentrations J Anal Toxicol.
1987;11(5):191-197.
17. Robertson MD, Drummer OH. Postmortem distribution and redistribution of nitrobenzodiazepines in man. J Forensic Sci. 1998;43(1):9-13.
18. Robertson MD, Drummer OH. Postmortem drug metabolism by bacteria J Forensic Sci. 1995;40(3):382-386.
19. Vorpahl TE, Coe JI. Correlation of antemortem and postmortem digoxin levels J Forensic Sci. 1978;23(2):329-334.
20. Yarema MC, Becker CE. Key concepts in postmortem drug redistribution Clin Toxicol (Phila). 2005;43(4):235-241.
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This ACS Webinar is a special rebroadcast of a past recording, there will be no slides available or interactive Q&A.
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