Dimetridazole Residues in Pork Tissue. II. Application of Liquid Chromatographic Method to Monitor Elimination of Drug and its Major Metabolite

Abstract

A study was conducted to monitor the elimination of dimetridazole (DMZ) and its major metabolite 2-hydroxymethyl-l-methyl-5-nitroimidazole (HMMNI) in swine plasma and tissue, using a liquid chromatographic method with electrochemical detector sensitive to 0.5 ppb. The study consisted of 2 experiments. In the preliminary experiment, one young female piglet was fed medicated ration containing 125 ppm dimetridazole (DMZ) for 2 weeks, followed by a withdrawal period using regular ration for 5 days. Another, control, piglet was given regular diet throughout. Plasma concentrations of DMZ and its most important residue, HMMNI, were measured daily at 2 h after the morning feeding and, on days 8 and 15, several times during the day. The 2 h concentrations after 3 days loading ranged from 47 to 77 ppb for DMZ and 424 to 1081 ppb for HMMNI. A daily cycle in the plasma levels was seen for both substances. Upon withdrawal of medication, elimination of drug and metabolite was biexponential with a terminal half-life of 6.7 h. In the second experiment, 5 piglets were medicated as above and slaughtered 2, 6, 12,25, and 49 h after withdrawal of the medication; the concentration of DMZ and HMMNI was measured in plasma, muscle, kidney, and liver. DMZ in the plasma amounted to 22 and 1.8 ppb at 2 and 6 h, while HMMNI declined from 535 ppb at 2 h to 0.75 ppb at 25 h. Most values for both substances found in muscle were close to those in the plasma; in kidney they amounted to 9-17% of the plasma levels. Very little HMMNI and no DMZ was found in the liver at 2 h. No drug or metabolite could be detected at 49 h in any of the tissues studied

Evaluation of public and animal health risks in case of a delayed post‐mortem inspection in ungulates

“…These results were confirmed in a study by Carignan et al. (1988). The concentration of HMMNI was measured in plasma, muscle, kidney and liver of pigs exposed to medicated feed (125 mg/kg).…”

“…In swine, residues of dimetridazole deplete rapidly during 24 h to levels below 1 lg/kg (Newkirk et al, 1990). These results were confirmed in a study by Carignan et al (1988). The concentration of HMMNI was measured in plasma, muscle, kidney and liver of pigs exposed to medicated feed (125 mg/kg).…”

Determination of nitroimidazole residues in poultry tissues, serum and eggs by high‐performance liquid chromatography

“…(1990) developed a method for determination of DMZ and its metabolite in swine muscle with gas chromatography (GC). Determination of DMZ and MNZ residues in animal tissue by high performance liquid chromatography (HPLC) with UV or electrochemical detection was described by Hobson-Frohoch (1983), Carignan et al (1988) and Aerts et al (1991. In most cases a multiple liquid-liquid extraction is used for sample clean-up.…”

Biotransformation of Dimetridazole by Primary Cultures of Pig Hepatocytes

“…Two metabolites have been identified in tissues and plasma of pigs (Figure 1). The major one, originally identified in turkeys (Law et al, 1963), is 1-methyl-2-hydroxymethyl-5-nitroimidazole (Carignan et al, 1988;Shaw et al, 1990), resulting from the hydroxylation of the 2-methyl group. A second minor metabolite was shown to be 2-methyl-(4,5)-nitroimidazole (Carignan et al, 1988(Carignan et al, , 1991, resulting from the N-demethylation of the drug.…”

“…The major one, originally identified in turkeys (Law et al, 1963), is 1-methyl-2-hydroxymethyl-5-nitroimidazole (Carignan et al, 1988;Shaw et al, 1990), resulting from the hydroxylation of the 2-methyl group. A second minor metabolite was shown to be 2-methyl-(4,5)-nitroimidazole (Carignan et al, 1988(Carignan et al, , 1991, resulting from the N-demethylation of the drug. On the basis of levels in feces and urine, the parent compound and these two metabolites appear to account for only a small part (< 5%) of the excreted drug (Shaw et al, 1991).…”