Postmortem Distribution of Heroin Metabolites in Femoral Blood, Liver, Cerebrospinal Fluid, and Vitreous Humor*

Abstract

The presence of 6-monoacetylmorphine (6-MAM) is often used to distinguish between heroin (diacetylmorphine) and morphine exposures. 6-MAM, however, is rapidly metabolized to morphine and may not be present in detectable quantities in blood following heroin exposure. Recent studies have shown that 6-MAM may persist in cerebrospinal fluid (CSF) and this specimen may be preferable for establishing heroin exposure. This study reports postmortem distribution of 6-MAM, unconjugated morphine, and codeine in different tissues from 25 deceased individuals. In all cases, 6-MAM was detected in vitreous humor, and in CSF in 16 of the 25 cases (64%). When 6-MAM was detected in blood (13 of 25 cases), the level of 6-MAM in vitreous humor and CSF was higher than in blood, with a mean concentration ratio of 11.3 (range: 1.7-27) for vitreous humor and 6.6 (range: 2.6-17.3) for CSF. 6-MAM was not detected in liver in any of the cases examined. Free morphine levels were highest in liver, followed by blood, CSF, and vitreous humor. The concentration ratios (mean +/- standard deviation) for free morphine in vitreous humor, CSF, and liver to that in blood were 0.36 +/- 0.18, 0.64 +/- 0.27, and 2.99 +/- 2.12, respectively. The liver/blood ratio was consistent with previously reported values for morphine in heart and femoral blood. Codeine levels following heroin overdose were consistently low relative to the morphine concentration. For blood, liver, and CSF, the ratio of codeine to morphine was essentially the same (0.06), whereas the vitreous codeine/morphine concentration ratio was slightly higher (0.19). These results characterize the distribution of heroin metabolites in postmortem tissues. Vitreous humor appears to be a useful specimen for determining 6-MAM and establishing the morphine was derived from heroin.

Vitreous Humor: A Short Review on Post-mortem Applications

“…Several reports have demonstrated that finding codeine to morphine ratio (C/M) less than 1 in blood or VH provides a good indication of heroin use [112][113][114][115][116][117]. In all of the heroin related deaths investigated in one present study, C/M ratios in blood and VH were less than 1, consistent with heroin exposure [111].…”

L’humeur vitrée en toxicologie médico-légale : revue de la littérature et applications

“…Les concentrations en morphine dans l'HV représentent environ un tiers de celles retrouvées dans le sang. Pour la codéine, les concentrations sont sensiblement équivalentes dans les deux milieux, le ratio HV/sang s'établissant à 1,03 [3].…”

“…En effet, diverses publications ont montré que la 6-MAM est plus facilement détectable dans l'HV que dans le sang. Dans une série de 13 cas en 2004, le ratio HV/sang des concentrations en 6-MAM était de 11,3 [3]. Cela n'inclut que les cas où la 6-MAM était détectable à la fois dans le sang et l'HV.…”

“…D'autres études ont aussi pu tester l'intérêt de l'HV pour le dosage de diverses drogues ou médicaments. Le dosage des opiacés notamment peut être intéressant en cas de suspicion d'overdose [3]. La diffusion et la stabilité de la cocaïne et de la benzoylecgonine ont aussi été étudiées [4].…”

Avaliação da redistribuição postmortem de opiáceos através de determinação em humor vítreo e sangue cardíaco e periférico humanos

“…Heroin is quickly metabolised to 6-acetylmorphine (6-AM), and the main metabolite detection allows the statement of heroin ingestion. However, 6-AM is also rapidly metabolised to morphine, which can make its detection difficult in many cases [7]. This metabolite is unstable in blood samples due to conversion to morphine by the action of esterases.…”