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Heroin-Related Compounds and Metabolic Ratios in Postmortem Samples Using LC-MS-MS
Gerd Jakobsson1,2, Michael T Truver1, Sonja A Wrobel2
1Division of Drug Research, Department of Biomedical and Clinical Sciences, Faculty of Medicine, Linköping University, 581 83, Linköping, Sweden.
Journal of Analytical Toxicology
|October 8, 2020
Summary
Analyzing morphine in postmortem samples is complex due to tolerance. This study developed a method to quantify opioid metabolites in urine, aiding interpretation of drug-related deaths and identifying abstinence periods.
Area of Science:
- Forensic toxicology
- Analytical chemistry
- Pharmacokinetics
Background:
- Interpreting postmortem morphine levels is challenging due to tolerance, complicating intoxication and cause of death assessments.
- Opioid metabolite analysis and metabolic ratios offer potential to distinguish between drug abstinence, continuous use, and timing of administration.
Purpose of the Study:
- To develop and validate a liquid chromatography-tandem mass spectrometry method for quantifying key opioid metabolites and parent drugs in urine.
- To apply this method to forensic cases involving opiate-related deaths.
- To compare metabolic ratios across different causes of death and drug intake scenarios, and differentiate rapid versus delayed heroin intoxication deaths.
Main Methods:
- Developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for analyzing morphine-3β-D-glucuronide, morphine-6β-D-glucuronide, normorphine, codeine-6β-D-glucuronide, norcodeine, codeine, 6-acetylmorphine, and ethylmorphine in urine.
- Analyzed 135 autopsy cases with paired blood and urine samples, categorizing by cause of death and drug intake (codeine, heroin, morphine, ethylmorphine).
- Compared metabolic ratios (e.g., morphine-3β-D-glucuronide/morphine) and drug concentrations in urine and blood between different case groups, including rapid vs. delayed heroin deaths.
Main Results:
- The validated LC-MS/MS method demonstrated acceptable precision, bias, and stability, with low limits of quantitation (0.01-0.2 μg/mL).
- Significant differences in metabolic ratios were observed between codeine versus morphine (p=0.005) and codeine versus heroin (p≤0.0001) intakes.
- Heroin intoxications showed significant differences in morphine, codeine, and 6-acetylmorphine concentrations in urine and morphine in blood between rapid and delayed deaths, though metabolic ratios did not differ significantly. Morphine-3β-D-glucuronide results indicated prior abstinence in 25% of heroin intoxication cases.
Conclusions:
- The validated LC-MS/MS method is suitable for quantifying opioid analytes in postmortem urine samples.
- Metabolic ratios in urine can help differentiate between various opioid intakes (codeine, heroin, morphine).
- Analysis of morphine-3β-D-glucuronide in urine may suggest a period of abstinence preceding death in some heroin users.
