Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose

Abstract

The postmortem distribution of morphine and its metabolites was investigated in four cases of heroin overdose to evaluate some of the factors that influence intravasal blood concentrations. Variables included were the chemical stability of morphine conjugates, hemoconcentration, incomplete distribution of the drug and diffusion processes. Blood samples from different sampling sites including the aorta, the infra- and suprarenal portion of the inferior vena cava, the superior vena cava, the femoral and subclavian veins, and the right and left ventricles were examined for morphine, morphine-3-glucuronide and morphine-6-glucuronide, hematocrit and water content. Drug concentrations were determined by HPLC based on the native fluorescence of the analytes. Morphine glucuronides proved to be stable for a time period of 72 h. The water content ranged from 65 to 83% and hematocrit values from 25 to 75%, and were seen as contributory factors to the dramatic differences observed for drug concentrations from different sampling sites. The differences could neither be attributed to incomplete distribution during life-time nor to a diffusion process following the different distribution volumes of morphine and its conjugates. A definite relationship between the ratio of the molar concentrations of morphine and its glucuronides, as assessed in pharmacokinetical studies after morphine dosing, could not be established. For a better understanding more cases and changes over time and tissue concentrations should be analysed.

Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h

“…A limited number of studies have investigated the glucuronide metabolites of morphine [50,51]. In this study we also studied the concentration changes of M3G over time in various matrices.…”

Stability of morphine and buprenorphine in whole blood

“…A false positive morphine in putrefied tissue due to the presence of putrefactive products has been reported [7]. A recent report on morphine conjugate stability showed that morphine glucuronides are stable for a few days [8] and controversial data exist concerning the stability of morphine in urine samples [9,10]. Buprenorphine is a recently marketed opiate and most of the published work relates either to the pharmacokinetics [11,12] or analysis [13][14][15][16].…”

Fatal injections of heroin. Interpretation of toxicological findings in multiple specimens

“…Thus, morphological changes in the lungs [21] and at the injection sites [22] in fatal and non-fatal overdose cases have been investigated. Furthermore, the impact of the morphine-6-glucuronide and morphine-3-glucuronide to free morphine ratios has been explored by some authors [6,11,15,23]. Although some of these reports also include analytical data from different sampling sites, this information has not been used for the determination of the injection site.…”

“…The extensive variation in concentrations found in deaths attributed to heroin intoxication may be explained by differences in samples used (e.g. central vs peripheral blood) [7,[9][10][11], differences in tolerance [5,12,13] and the time interval between injection and death [5,6,11,[14][15][16]. The simple fact that an intentional overdose, when injected, may exceed the fatal dose severalfold will also contribute to the wide interindividual variation in postmortem blood concentrations.…”