Abstract

Metronidazole (MNZ) is used in veterinary medicine for the treatment of anaerobic infections and a variety of protozoal and parasitic diseases. Current study has been conducted to examine the disposition and residue depletion studies of MNZ and its main metabolites in pigs and broilers. After a single oral administration of MNZ, the concentrations of MNZ and its main metabolites in the excreta of pigs and broilers were determined by LC-MS/MS. More than 75% of the drug was recovered within 14 days, of which MNZ accounted for about 40%, MNZ-OH 20–25% and MAA less than 10%. The residue depletion study showed that MNZ was the most predominant residue in all of the tissues and could be detected in liver, kidney and muscle up to the withdrawal time of 14 days. MNZ-OH concentrations were lower than MNZ in all of the tissues, but its elimination half-life was close to MNZ. It is proposed that kidney and muscle are appropriate residue target tissues and both MNZ and its hydroxylated metabolite, MNZ-OH, should be monitored in the routine surveillance of MNZ related residues in food of animal origin.

Highlights

  • Metronidazole (MNZ, 1-(hydroxyethyl)-2-methyl-5-nitroimidazole) is an antimicrobial agent which is especially used to treat anaerobic bacterial infection, protozoal and parasitic diseases[1]

  • A total of 80.3 ± 5.9% of the administrated drug was recovered over a period of 14 days of which about 70% were collected in 24 h (Fig. 1)

  • Besides MNZ, its two oxidation metabolites (MNZ-OH and methyl-5-nitroimidazole-1-acetic acid (MAA)) and two glucuronide conjugates were observed in the pigs urine

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Summary

Introduction

Metronidazole (MNZ, 1-(hydroxyethyl)-2-methyl-5-nitroimidazole) is an antimicrobial agent which is especially used to treat anaerobic bacterial infection, protozoal and parasitic diseases[1]. In a study on the disposition of 14C-MNZ in rats, four compounds, including MNZ, Glu-MNZ, MNZ-OH and 2-methyl-5-nitroimidazole-1-acetic acid (MAA) were identified as major metabolites[12]. The availability of data on MNZ residue depletion in pigs and broilers is limited and according to the guidance of VICH GL46 of FDA, a comprehensive residue depletion study should contain the parent drug and its main metabolites[15]. The residue depletion of MNZ and its major metabolites in tissues of pigs and broilers were investigated. Its metabolites in edible tissues (liver, kidney, muscle, fat etc.) of pigs and broilers should be useful for safety assessment of MNZ and offer a specific target and technical support for MNZ residue monitoring in foodstuffs of animal origin

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