POSTMORTEM DISTRIBUTION PATTERN OF MORPHINE AND MORPHINE GLUCURONIDESIN HEROIN OVERDOSE

The postmortem distribution of morphine and its metabolites was invest igated in four cases of heroin overdose to evaluate some of the factor s that influence intravasal blood concentrations. Variables included w ere the chemical stability of morphine conjugates, hemoconcentration, incomplete distribution of the drug and diffusion processes. Blood sam ples 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 w ere examined for morphine, morphine-3-glucuronide and morphine-6-glucu ronide, hematocrit and water content. Drug concentrations were determi ned 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 hematrocrit values from 25 to 75%, and were seen as contributory factors to the dramatic differences obse rved for drug concentrations from different sampling sites. The differ ences could neither be attributed to incomplete distribution during li fe-time nor to a diffusion process following the different distributio n volumes of morphine and its conjugates. A definite relationship betw een the ratio of the molar concentrations of morphine and its glucuron ides, as assessed in pharmacokinetical studies after morphine dosing, could not be established. For a better understanding more cases and ch anges over time and tissue concentrations should be analysed.