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The identification and assay of 2-methyl-5-nitroimidazole in pigs treated with dimetridazole
G Carignan1, K Carrier, S Sved
1Drug Residues Section, Bureau of Drug Research, Health and Welfare Canada, Ottawa, Ontario.
Abstract:
An unidentified metabolite of dimetridazole (DMZ), found in pig plasma, muscle and kidney, was shown by chromatography and spectroscopy to be 2-methyl-5-nitroimidazole (2-MNI), resulting from N-demethylation of DMZ. This route of degradation competes with the oxidation pathway previously described. The concentration of 2-MNI in the plasma of pig fed medicated diet (DMZ 0.0125%) ranged from 29 to 83 ppb, 2 hours after the morning meal, similar to DMZ, but lower than that of the major metabolite, 2-hydroxymethyl-1-methyl-5-nitroimidazole (HMMNI). Its elimination profile in plasma was biphasic, similar to those of HMMNI and DMZ. Early and terminal half lives were 2.6 and 9.1 h respectively. None of the metabolites could be detected in any of the tissues studied 49 hours after withdrawal.
Insights
A new metabolite of dimetridazole (DMZ), 2-methyl-5-nitroimidazole (2-MNI), was identified in pigs. This N-demethylation product is present in plasma and tissues, with a biphasic elimination profile.
Area of Science:
- Veterinary Pharmacology
- Drug Metabolism Studies
- Analytical Chemistry
Background:
- Dimetridazole (DMZ) is a veterinary drug with known metabolites.
- Understanding DMZ metabolism is crucial for food safety and animal health.
- Previous studies identified an oxidation pathway for DMZ degradation.
Purpose of the Study:
- To identify an unknown metabolite of dimetridazole (DMZ) found in pig tissues.
- To characterize the metabolic pathway and pharmacokinetic properties of this new metabolite.
- To compare its concentration and elimination with DMZ and other known metabolites.
Main Methods:
- Chromatography and spectroscopy were employed for metabolite identification.
- Quantification of metabolites in pig plasma and tissues.
- Pharmacokinetic analysis including half-life determination.
Main Results:
- The unidentified metabolite was identified as 2-methyl-5-nitroimidazole (2-MNI), formed via N-demethylation of DMZ.
- 2-MNI was detected in pig plasma, muscle, and kidney.
- Plasma concentrations of 2-MNI ranged from 29 to 83 ppb, with biphasic elimination (early half-life 2.6 h, terminal half-life 9.1 h).
- No metabolites were detected in tissues 49 hours post-withdrawal.
Conclusions:
- N-demethylation is a significant metabolic pathway for DMZ in pigs, competing with oxidation.
- 2-MNI is a relevant metabolite with specific pharmacokinetic characteristics in pigs.
- Further research may be needed to fully assess the toxicological implications of 2-MNI.