Distribution, pharmacokinetics and primary metabolism model of tramadol in zebrafish

Zhuo,Huiqin; Jin,Hongwei; Peng,Huifang; Huang,Heqing

doi:10.3892/mmr.2016.5956

Distribution, pharmacokinetics and primary metabolism model of tramadol in zebrafish

Authors:
- Huiqin Zhuo
- Hongwei Jin
- Huifang Peng
- Heqing Huang
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Affiliations: Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P.R. China, Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361005, P.R. China, State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, Xiamen, Fujian 361005, P.R. China
Published online on: November 21, 2016 https://doi.org/10.3892/mmr.2016.5956
Pages: 5644-5652

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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.

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