Dynamic Distribution and Postmortem Redistribution of Tramadol in Poisoned Rats

Abstract

Abstract In the past dozen years, the cases of tramadol intoxication have become frequent in many countries. Most previous studies focused on tramadol’s pharmacology, such as pharmacokinetics, pharmacodynamics and pharmacogenetics. However, the dynamic distribution and postmortem redistribution (PMR) of tramadol remain unclear. Our study aimed to investigate these two issues systematically in various specimens of 216 poisoned male rats. A validated gas chromatography–mass spectrometry method was used in this study to measure the concentrations of tramadol. In the first part, 66 tramadol poisoned rats were sacrificed at 11 different time points and their organs were collected separately for the study of tramadol’s dynamic distribution, which made it feasible to investigate its PMR later on. The results of this part showed that tramadol’s concentrations varied according to the organ and time, and peaked 2 h after intragastric administration in the specimens of liver, kidney, spleen, lung, brain and heart-blood (except stomach and heart). Based on the results of the first part, the concentration of tramadol peaked 2 h in most tissues. Therefore, this time point was used for the study of tramadol’s PMR. In the second part, the remaining 150 rats were sacrificed 2 h after intragastric administration of tramadol, and the carcasses were stored under three different conditions (−20, 4 and 20°C). The autopsy was carried out at eight different time points and their organs were collected separately. The results of this part showed that under storage temperatures of −20 and 4°C, the concentrations of tramadol in individual organs showed no significant changes at different time points whereas under a storage temperature of 20°C, the concentrations in certain organs (liver, kidney, spleen, lung, brain and heart-blood) increased significantly at the last few time points. PMR of tramadol was therefore confirmed. The process of PMR of tramadol could be slowed or stopped at lower storage temperatures (−20 or 4°C), which is significant in cases of suspected tramadol poisoning.