title: Tissue residues and urinary excretion of zilpaterol in sheep treated for 10 days with dietary zilpaterol.
abstract: Zilpaterol is a beta-adrenergic growth promoter approved in Mexico and South Africa for use in cattle. Understanding the rates of zilpaterol depletion from tissues and urine is of interest for the development of strategies to detect the off-label use of zilpaterol. Eight sheep were fed 0.15 mg/kg/day dietary zilpaterol hydrochloride (Zilmax) for 10 consecutive days; two sheep each were slaughtered 0, 2, 5, and 9 days after discontinuation of exposure to the zilpaterol-containing diet. Tissue zilpaterol levels rapidly decreased during the withdrawal period. On the basis of LC-MS/MS-ES (external standard) measurements, liver zilpaterol residues in sheep were 29.3, 1.5, 0.13, and 0.10 ng/g after 0, 2, 5, and 9 day withdrawal periods, respectively; kidney residues were 29.6, 1.10, and 0.09 ng/g and below the detection limit; and muscle residues were 13.3, 0.86, 0.12, and 0.08 ng/g at the same respective withdrawal periods. Between-animal variation in urinary zilpaterol concentrations during the feeding period was considerable, although zilpaterol concentrations converged somewhat as steady state was reached. During the first 3 days of the withdrawal period, zilpaterol elimination followed a first-order excretion pattern, having an average elimination half-life of 15.3 +/- 1.8 h. Urinary zilpaterol concentrations during the withdrawal period were determined using ELISA, HPLC-fluorescence, LC-MS/MS-ES (external standard), and LC-MS/MS-IS (internal standard). Comparison of these methods showed a high correlation with each other. With the exception of LC-MS/MS-IS, the regression coefficients of the linear equations with a zero intercept were between 0.90 and 1.25, indicating the near equivalence of the methods. Because of its simplicity, ELISA is a convenient assay for determining zilpaterol levels in urine giving similar results to HPLC-fluorescence and LC-MS/MS-ES without requiring the extensive cleanup of the latter methods.
authors.affiliation: Biosciences Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, 1605 Albrecht Boulevard, Fargo, North Dakota 58105, USA. shelverw@fargo.ars.usda.gov
authors.forename: Weilin L
authors.initials: WL
authors.lastname: Shelver
authors.forename: David J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D013058:Mass Spectrometry; D018482:Muscle, Skeletal / Q000737:chemistry; D012756:Sheep / Q000378:metabolism* / Q000652:urine; D014297:Trimethylsilyl Compounds / Q000008:administration & dosage* / Q000032:analysis* / Q000652:urine
chemical_list: D014297:Trimethylsilyl Compounds; C475840:Zilpaterol