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Liver and blood postmortem tricyclic antidepressant concentrations
1Clinical Laboratories, Hennepin County Medical Center, Minneapolis, Minnesota 55415.
American Journal of Clinical Pathology
|June 1, 1988
Summary
Tricyclic antidepressant (TCA) overdoses are a significant cause of poisoning deaths. Postmortem blood TCA levels can be misleading due to tissue release, suggesting liver levels are more reliable for determining manner of death.
Area of Science:
- Forensic Toxicology
- Clinical Chemistry
- Pharmacology
Background:
- Tricyclic antidepressants (TCAs) are a leading cause of fatal drug ingestions.
- TCAs exhibit high tissue binding, leading to the hypothesis of postmortem blood level elevation from tissue release.
Purpose of the Study:
- To evaluate the reliability of postmortem blood and liver tricyclic antidepressant (TCA) levels in determining cause of death.
- To analyze the relationship between postmortem interval and TCA blood levels.
Main Methods:
- Quantification of postmortem liver and blood TCA levels (parent drug and active metabolite) using high-pressure liquid chromatography (HPLC) and gas chromatography mass spectrometry (GC-MS).
- Comparison of TCA levels in overdose cases versus cases with therapeutic TCA ingestion.
Main Results:
- TCA overdose deaths remained constant as a percentage of total poisoning deaths from 1977-1985.
- A significant increase in blood TCA levels was observed with increasing postmortem interval.
- Mean liver TCA levels were substantially higher than blood levels in both overdose (232 µg/g vs. 6.2 mg/L) and therapeutic (10.8 µg/g vs. 0.26 mg/L) cases, with similar liver-to-blood ratios (37:1 and 39.2:1, respectively).
Conclusions:
- Elevated postmortem blood TCA levels can be falsely indicated by postmortem tissue release, potentially misrepresenting the manner of death.
- The large tissue-to-blood gradient suggests that liver TCA levels are a more accurate indicator of TCA ingestion and manner of death than blood levels.