Unexpected Variation of the Codeine/Morphine Ratio Following Fatal Heroin Overdose

Abstract

Postmortem samples from 14 cases of suspected heroin overdose were subjected to a preliminary systematic toxicological analysis in order to highlight the presence of unknown exogenous compounds (e.g., drugs of abuse, alcohol) that may have played a role in the mechanism of death. This analysis unveiled histories of poly-drug use in seven of the cases under investigation. Moreover, the concentrations of morphine and codeine in the brain were also investigated, and the results were compared with the data obtained from the blood specimens. The concentration of morphine in blood ranged from 33 to 688 ng/mL, while the concentration of codeine ranged from 0 to 193 ng/mL. However, in the brain, the concentration of morphine was found to be between 85 and 396 ng/g, while the levels of codeine ranged from 11 to 160 ng/g. The codeine/morphine ratio in the blood ranged from 0.043 to 0.619; however, in the brain, the same ratio was found to be between 0.129 and 0.552. In most cases, a significantly higher codeine/morphine ratio was found in the brain, suggesting the accumulation of codeine in brain tissue due its high lipophilicity as compared with morphine.

Determination of 6-Monoacetyl-Morphine (6-MAM) in Brain Samples from Heroin Fatalities

“…In order to evaluate the distribution of morphine and codeine in the brain, in a previous study [11] a GC/MS method was applied to the determination of morphine and codeine levels in nuclei specimens from fourteen fatal cases of suspected heroin overdose. In this work, we focused our attention on the detection of 6-MAM in eight cases considered in the previous paper, of which a sufficient quantity of brain tissue was still available (cases 1-8).…”

“…In these samples also the levels of morphine and codeine were evaluated. Moreover we analyzed other seven samples from heroin fatalities belonging to a period of time between 2012 and 2014 (cases [9][10][11][12][13][14][15]. To this end we studied and validated an analytical method suitable to this purpose, using deuterated internal standards in order to enhance sensitivity (Figure 1).…”

“…The subjects were mainly men aged between 23 and 56 years (mean 39 years), and circumstantial evidence suggested that the deaths in each case were heroin related. Eight samples (cases 1-8) belonged to people died between 2008 and 2011 and they were analyzed also in 2012 to establish morphine and codeine levels [11]. Seven samples belonged to people died between 2012 and 2014 and they were analyzed for the first time.…”

“…In a previous study [10], we developed a gas chromatography/mass spectrometry (GC/MS) method to investigate the brain distribution patterns of morphine and codeine, which was then, applied to the determination of their levels in nuclei specimens from 14 fatal cases of suspected heroin overdose. The results of this analysis were subsequently compared to metabolite levels in the blood obtained from the systematic toxicological analysis (STA) [11]. In this work we focused our attention on the detection of 6-MAM, whose presence is extremely important to discriminate between heroin abuse and therapeutic use of morphine [12][13][14][15].…”

“…Analyses were performed in fifteen brain samples from heroin fatalities belonging to a period of time between 2008 and 2014. The first eight samples were also analyzed in 2012 [11] to determine morphine and codeine levels. The other seven cases were analyzed for the first time.…”