title: 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-1-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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Health and Welfare Canada, Bureau of Drug Research, Ottawa, Ontario.
authors.forename: G
authors.initials: G
authors.lastname: Carignan
authors.forename: A I
authors.initials: AI
authors.lastname: MacIntosh
authors.forename: W
authors.initials: W
authors.lastname: Skakum
authors.forename: S
authors.initials: S
authors.lastname: Sved
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D001711:Biotransformation; D002853:Chromatography, Liquid; D004131:Dimetridazole / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D004350:Drug Residues / Q000032:analysis*; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood; D009593:Nitroimidazoles / Q000032:analysis*; D013552:Swine
chemical_list: D009593:Nitroimidazoles; D008795:Metronidazole; C059098:2-hydroxymethyl-1-methyl-5-nitroimidazole; D004131:Dimetridazole