title: Distribution, pharmacokinetics and primary metabolism model of tramadol in zebrafish.
abstract: 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 µg) 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 µg) 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.
authors.affiliation: Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zhuo
authors.affiliation: Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D021241:Spectrometry, Mass, Electrospray Ionization; D014018:Tissue Distribution; D014147:Tramadol / Q000493:pharmacokinetics*; D015027:Zebrafish
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol