13th International Drug Chemistry Conference (13th DCC), Antalya, Türkiye, 6 - 09 Şubat 2025, ss.256
The FDA has authorized Tramadol, a synthetic opioid analgesic, for moderate to severe pain. Tramadol was categorized as a Schedule IV prohibited substance by the FDA in July 2014 because of its abuse, dependency, and misuse. The opioid pandemic raises concerns regarding low-dose tramadol misuse, addiction, and long-term dependency. Illegal tramadol use increases addiction risk. Even people who strictly follow their doctor's orders may become dependent on the drug. Postmortem distribution is the redistribution of drugs, poisons, and other chemicals in the body's tissues and fluids. Postmortem physiological changes and tissue biology affect this process. The postmortem distribution of tramadol is essential for determining death causes and drug concentrations. Our study aimed to investigate the postmortem distribution of tramadol in various tissues. To achieve this, a method was developed to detect and quantify tramadol in liver, lung, heart, spleen, brain, and kidney tissues obtained from sacrificed rats. The HPLC analysis was performed under the following optimized conditions: the mobile phase consisted of a mixture of 0,1 M pH 7,4 potassium phosphate buffer and acetonitrile (70:30; v/v). The separation was achieved using isocratic elution at a 1 mL/min flow rate. The column temperature was maintained at 25°C, and the injection volume was set to 20 µL. The detector wavelength was adjusted at 220 nm. After sacrificing the rats, samples were collected at 60, 120, 240, and 1440 minutes. Tramadol concentrations were measured in homogenized tissue samples, as presented in the table. At 60 minutes, the spleen exhibited the highest tramadol concentration (167.7 µg/mL), followed by the kidney (56.4 µg/mL) and lung (49.1 µg/mL). Over time, tramadol levels generally declined in most tissues, with notable exceptions. For instance, in the liver, tramadol levels initially decreased but showed a substantial increase at 240 and 1440 minutes, reaching 72 µg/mL at the final time point. In contrast, tissues such as the heart and spleen showed a rapid decline, with no detectable tramadol at 240 and 1440 minutes, respectively. The serum exhibited relatively low and stable tramadol levels throughout the study period. These findings suggest that tramadol distribution and persistence vary significantly among different tissues, with the liver demonstrating a potential for accumulation over extended periods.