Tissue distribution and residue depletion of metronidazole in rainbow trout (Oncorhynchus mykiss)

Abstract

Tissue distribution and residue depletion of metronidazole (MNZ) was studied in rainbow trout (Oncorhynchus mykiss) following oral administration of MNZ in feed at the average dose of 25 mg kg⁻¹ body weight day⁻¹ for 7 days at 11 ± 2°C. The MNZ concentration in feed was 0.25% while daily feed intake was 1% of body weight. The concentrations of MNZ and its main metabolite, hydroxymetronidazole (MNZOH), in fish tissues were determined by LC-MS/MS. The drug was well distributed in tissues with maximum concentrations on day 1 post-administration. At this time, the mean MNZ concentrations in muscle, skin, kidney, liver and gill were 14 999, 20 269, 15 070, 10 102 and 16 467 µg kg⁻¹ respectively. MNZ was converted into MNZOH with the ratio of MNZOH:MNZ up to 7% in all fish tissues throughout the withdrawal period. This shows that MNZ itself is the main residue in rainbow trout. MNZ was detected at the level close to the decision limit (0.20 µg kg⁻¹) in muscle, skin and muscle with adhering skin up to 42 days, while in kidney, liver and gill it was up to 28 days post-administration. MNZOH was eliminated more rapidly from fish tissues and it was present in muscle alone up to 21 days. The elimination half-lives of MNZ and MNZOH in rainbow trout tissues were 1.83–2.53 and 1.24–2.12 days, respectively. When muscle without skin was analysed, higher MNZ and MNZOH concentrations were detected, and for a longer period of time, than in muscle with adhering skin. Thus muscle alone could be more appropriate for the effective residue control of MNZ in rainbow trout. For the same reason, it is also essential to ensure direct cooling immediately after sampling, since MNZ and its metabolite degrade in fish muscle and skin stored in non-freezing conditions.

Graphical Abstract

Keywords:

• metronidazole
• tissue distribution
• residue
• depletion
• elimination half-life
• storage conditions
• rainbow trout
• LC-MS/MS