Postmortem tissue distribution of morphine and its metabolites in a series of heroin‐related deaths

Abstract

The abuse of heroin (diamorphine) and heroin-related deaths are increasing around the world. The interpretation of the toxicological results from suspected heroin-related deaths is notoriously difficult, especially in cases where there may be limited samples. To help forensic practitioners with heroin interpretation, we determined the concentration of morphine (M), morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) in blood (femoral and cardiac), brain (thalamus), liver (deep right lobe), bone marrow (sternum), skeletal muscle (psoas), and vitreous humor in 44 heroin-related deaths. The presence of 6-monoacetylmorphine (6-MAM) in any of the postmortem samples was used as confirmation of heroin use. Quantitation was carried out using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with solid-phase extraction. We also determined the presence of papaverine, noscapine and codeine in the samples, substances often found in illicit heroin and that may help determine illicit heroin use. The results of this study show that vitreous is the best sample to detect 6-MAM (100% of cases), and thus heroin use. The results of the M, M3G, and M6G quantitation in this study allow a degree of interpretation when samples are limited. However in some cases it may not be possible to determine heroin/morphine use as in four cases in muscle (three cases in bone marrow) no morphine, M3G, or M6G were detected, even though they were detected in other case samples. As always, postmortem cases of suspected morphine/heroin intoxication should be interpreted with care and with as much case knowledge as possible.

Summary statistics for drug concentrations in post‐mortem femoral blood representing all causes of death

“…Interest is currently focused on the quantification of drugs in PM materials other than blood, including bile, brain, liver, muscle, and vitreous humor . However, while these alternative materials show promising results with individual drugs or in specific circumstances, femoral venous blood still represents the most viable material for interpretative purposes in PM toxicology, with a more extensive range of reference concentrations published in the literature.…”

Postmortem Liver and Kidney Tissue Concentrations of Heroin Biomarkers and Their Metabolites in Heroin‐Related Fatalities*†

“…In addition, their extraction recovery was better than 70.0%. Other reported methods have measured total morphine after converting glucuronide conjugates of morphine to their free form with enzymatic hydrolysis (15,23) or have used direct determination of morphine and its glucuronide conjugates without hydrolysis using LC-MS-MS (24). In fact, few studies have reported the level of heroin metabolites in solid tissue specimens.…”

“…However, the method was not applied to real liver specimens collected from postmortem cases. To the author's knowledge, only one method has been reported for analyzing postmortem liver tissues with LC-MS-MS (24). In that method, liver concentrations were determined using calibration curves derived from plasma extraction.…”

“…Two quality controls consisting of spiked animal specimens were used to determine method accuracy and bias, which were within the acceptable range (AE15%). Solid-phase extraction with C18 SPE columns was used in both studies (24,26). To retain morphine's polar metabolites, suppression of matrix effects and recovery were calculated in liver samples and found to be 2% and 38%, respectively.…”

Drugs in bone: Detectability of substances of toxicological interest in different states of preservation

“…However, there are too many confounding factors, for example, bone irroration, chemical properties of the drug, individual tolerance and metabolism, etc. [1,3,6,9,13,16,23,26,46,49‐51 ] whose mechanisms are beyond the scope of this study.…”