Immunochemical-based zilpaterol measurement and validation in urine and tissues

Shelver, Weilin L.; Smith, David J.

doi:10.1080/09540105.2011.565038

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…Consistent with the observed adverse clinical responses in these horses, the initial urinary concentrations of Zilpaterol were estimated at about 10 times the concentrations reported in bovines and sheep [ 11 – 13 ] and 100 times the concentrations reported in pigs [ 13 ]. The basis of the pharmacokinetic differences between these species is unclear, but it is apparent that administered as a one-time oral dose, Zilpaterol is rapidly and completely absorbed by the horse, yields higher than expected plasma concentrations as judged by the adverse clinical responses reported, and is also excreted initially at relatively high concentrations in equine urine [ 10 , 14 ].…”

Section: Introductionsupporting

confidence: 79%

“…The Shelver equine studies [ 10 – 13 ] demonstrate the pharmacokinetic profile of Zilpaterol after a two dose regimen, which is unlikely to reflect the exposure of horses in our described “clusters” of urinary identifications resulting from ongoing trace level dietary exposure. To our knowledge the only available data on ongoing trace level dietary exposure in any animal are those of Smith et al, 2019, who studied the relationship between dietary exposure to trace amounts of Zilpaterol and urinary concentrations in sheep [ 12 ].…”

Section: Introductionmentioning

confidence: 94%

“…The best available data on post administration equine urinary concentrations of Zilpaterol are those of Shelver and colleagues [ 10 – 13 ]. In their equine experiments Zilpaterol was administered at the recommended food animal dose of 0.17 mg/kg of body weight, for a total daily dose of about 70 mg per horse to three horses weighing about 470 kg.…”

Section: Introductionmentioning

confidence: 99%

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Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis

Machin

Brewer²,

Morales-Briceño

et al. 2022

Ir Vet J

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Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary “identifications” of Zilpaterol. These “identifications” occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presents in horse urine, yielding clusters of feed related Zilpaterol identifications in racehorses. The first cluster, April 2013, involved 48 racehorses in California; the second cluster, July 2013, involved 15 to 80 racehorses in Hong Kong. The third cluster, March 2019, involved 24 racehorses in Mauritius; this cluster traced to South African feedstuffs, triggering an alert concerning possible Zilpaterol feed contamination in South African racing. The fourth cluster, September/October 2020 involved 18 or so identifications in French racing, reported by the French Laboratories des Courses Hippiques, (LCH), and in July 2021, a fifth cluster of 10 Zilpaterol identifications in South Africa.The regulatory approach to these identifications has been to alert horsemen and feed companies and penalties against horsemen are generally not implemented. Additionally, given their minimal exposure to Zilpaterol, there is little likelihood of Zilpaterol effects on racing performance or adverse health effects for exposed horses.The driving factor in these events is that Zilpaterol is dissolved in molasses for incorporation into cattle feed. Inadvertent incorporation of Zilpaterol containing molasses into horse feed was the source of the California and Hong Kong Zilpaterol identifications. A second factor in the 2019 Mauritius and 2020 French identifications was the sensitivity of testing for Zilpaterol in Mauritius and France, with the French laboratory reportedly testing at a “more sensitive level for Zilpaterol”. As of January 1st, 2021, the new FEI Atypical Finding (ATF) policy specifies Zilpaterol as a substance to be treated as an Atypical Finding (ATF), allowing consideration of inadvertent feed contamination in the regulatory evaluation of Zilpaterol identifications.

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Section: Introductionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis

Machin

Brewer²,

Morales-Briceño

et al. 2022

Ir Vet J

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“…Animals excrete relatively high concentrations of zilpaterol in urine during times of active exposures at production-enhancing doses. For example, data in Table 4 confirm that urinary concentrations of zilpaterol typically exceed 1,000 ng mL −1 (Stachel et al 2003;Shelver and Smith 2006) and sometimes exceed 10,000 ng mL −1 in urine from animals during zilpaterol exposure (Shelver and Smith 2011). In the current study, the greatest urinary zilpaterol concentrations were 200 to 400 ng mL −1 during active feeding at zilpaterol concentrations one-tenth the label dose.…”

Section: Discussionmentioning

confidence: 94%

Detection and quantification of residues in sheep exposed to trace levels of dietary zilpaterol HCl

Smith

Shelver

Chakrabarty

et al. 2019

Food Additives & Contaminants: Part A

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Study objectives were to determine zilpaterol residues in urine and tissues of sheep fed dietary zilpaterol HCl, at levels commensurate with feed contamination, using common and novel screening and quantitative analytical methods. Sheep (50.0 ± 2.7 kg) were offered feed (1.75 kg/d) containing 0.0075 (L), 0.075 (M), or 0.75 (H) mg kg −1 of zilpaterol for 12 days and were slaughtered with 0-day (L-0, M-0, H-0; n = 4 each) or 3-day (H-3; n = 4) withdrawal periods. Rapid immunochromatographic assays (ICA) consistently detected urinary zilpaterol (LOD = 1.7 ng mL −1) in L-0 (54.2%), M-0 (96.0%), and the H-0 (100%) treatment groups but only detected zilpaterol in tissues (LOD~2.4 ng g −1) from the H-0 group. Advanced MS-based technologies detected zilpaterol in some, but not all, tissues of M-0, H-0, L-0, and H-3 sheep. Analytical techniques commonly used to ensure compliance with show-animal rules, import/export guidelines, and regulatory statutes routinely detected residues in animals exposed to zilpaterol at doses insufficient to elicit growth responses.

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“…Immunoassays ( Shelver et al ., 2005 ; Shelver and Smith, 2011 ), high-performance liquid chromatography (HPLC) ( Freire et al ., 2013 ; Zhao et al ., 2010 ), gas chromatography-mass spectrometry (GC-MS) ( Wang et al ., 2010 ), and liquid chromatography-mass spectrometry (LC-MS) ( Zhang et al ., 2009 ) have been used to analyze β-agonist residues. Recently, liquid chromatography-tandem mass spectrometry (LC/MS/MS) has been commonly used since it can quantitatively and qualitatively analyze a substance based on the unique characteristics of mass and fragment ions created by an electrical current ( Juan et al ., 2010 ; Li et al ., 2010 ; Shao et al , 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Development and Application of a Method for Rapid and Simultaneous Determination of Three β-agonists (Clenbuterol, Ractopamine, and Zilpaterol) using Liquid Chromatography-tandem Mass Spectrometry

Sung¹,

Park²,

Kang³

et al. 2015

Korean Journal for Food Science of Animal Resources

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β-agonists are anabolic compounds that promote fat loss and muscle gain, and their administration to livestock may provide economic benefits by increasing growth rate and feed efficiency. For these reasons, β-agonists are also commonly added to livestock feed as growth promoters. This can introduce a significant risk of secondary human poisoning through intake of contaminated meat. A new method for the simultaneous determination of three β-agonists (clenbuterol, ractopamine, and zilpaterol) was developed in this study and applied to various meat samples. The limits of quantification, derived through a validation test following Codex guidelines, were 0.2 μg/kg for clenbuterol and zilpaterol, and 0.4 μg/kg for ractopamine. The average recoveries for clenbuterol, ractopamine, and zilpaterol ranged from 109.1% to 118.3%, 95.3% to 109.0%, and 94.1% to 120.0%, respectively. The recovery and coefficient of variation (CV) values fell within the acceptable range according to the Codex guidelines. This method reduced the analysis time without decreasing detection efficiency by modifying the pretreatment steps. This method could be utilized to manage the safety of imported meat products from countries where zilpaterol use is still permitted, thereby improving public health and preventing β-agonist poisoning due to secondary contamination.

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Immunochemical-based zilpaterol measurement and validation in urine and tissues

Cited by 7 publications

References 20 publications

Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis

Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis

Detection and quantification of residues in sheep exposed to trace levels of dietary zilpaterol HCl

Development and Application of a Method for Rapid and Simultaneous Determination of Three β-agonists (Clenbuterol, Ractopamine, and Zilpaterol) using Liquid Chromatography-tandem Mass Spectrometry

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