Distribution, pharmacokinetics and primary metabolism model of tramadol in zebrafish

The current study aimed to develop a rapid, robust and adequately sensitive method for simultaneous determination of the concentration of tramadol and its active metabolites in zebrafish. The pharmacokinetic and elimination pattern of tramadol and its major phase I metabolites following oral or intramuscular administration in zebrafish tissues was achieved using electrospray ionization-quadrupole-time of flight/mass spectrometry (ESI-Q-TOF/MS) and gas chromatography/mass spectrometry (GC-MS). Following administration, the metabolisms were detected in the brain, eyes, muscle and gill tissues within 1 h. Two tramadol metabolites, O- and N-desmethyltramadol, were detected in brain tissue, with N-desmethyltramadol detected at a higher level. Following GC-MS detection the curve indicated an initial rapid phase, corresponding to the detection of the tramadol within 1 min, and reached peak value in the brain at 5 min. Faster drug clearance was detected in low-dose groups, and concentration had dropped around the to initial level (1.11 mu g) at 20 min, but was detectable for up to 3 h. However, it took 80 min to fall back to the initial value (1.73 mu g) in the high-dose groups, and tramadol was detectable for up to 4 h. This study developed and validated a simple and high throughput analytical procedure to determine the distribution and pharmacokinetic profiles of tramadol, and its primary metabolites in tissues of zebrafish.